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51.428571 0 0 51.428571 0 1250.362319 Tm 6.358333 0 Td 50.771605 Tz (generates ) Tj 2.916667 0 Td 55.740741 Tz (LPA\). ) Tj 1.866667 0 Td 71.296296 Tz (LPA ) Tj 1.419444 0 Td 52.932099 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.516667 0 Td 47.800926 Tz (realized ) Tj 2.45 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 48.935185 Tz (contribute ) Tj 3.072222 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 58.333333 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 1212.400955 Tm 6.358333 0 Td 43.75 Tz (cell ) Tj 1.205556 0 Td 52.777778 Tz (growth, ) Tj 2.372222 0 Td 48.148148 Tz (unfortunately, ) Tj 4.180556 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 45.046296 Tz (reactivity ) Tj 2.877778 0 Td 50.771605 Tz (within ) Tj 1.963889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 68.055556 Tz (human ) Tj 51.428571 0 0 51.428571 0 1166.767263 Tm 6.338889 0 Td 60.763889 Tz (body ) Tj 1.711111 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 71.296296 Tz (LPA ) Tj 1.555556 0 Td 50.771605 Tz (within ) Tj 2.1 0 Td 46.759259 Tz (certain ) Tj 2.236111 0 Td 45.833333 Tz (tissues ) Tj 2.177778 0 Td 54.012346 Tz (has ) Tj 1.263889 0 Td 45.730453 Tz (resulted, ) Tj 2.722222 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 48.148148 Tz (certain ) Tj 51.428571 0 0 51.428571 0 1126.239609 Tm 6.377778 0 Td 45.37037 Tz (studies, ) Tj 2.391667 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 53.652263 Tz (cancerous ) Tj 3.072222 0 Td 55.555556 Tz (growths ) Tj 2.527778 0 Td 64.814815 Tz (when ) Tj 1.730556 0 Td 50.462963 Tz (present ) Tj 2.294444 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 43.055556 Tz (levels. ) Tj 51.428571 0 0 51.428571 0 1084.044335 Tm 6.377778 0 Td 48.611111 Tz (In ) Tj 0.738889 0 Td 43.75 Tz (this ) Tj 1.225 0 Td 55.092593 Tz (manner, ) Tj 2.488889 0 Td 47.314815 Tz (then, ) Tj 1.594444 0 Td 32.407407 Tz (it ) Tj 0.525 0 Td 54.012346 Tz (has ) Tj 1.108333 0 Td 57.523148 Tz (been ) Tj 1.555556 0 Td 50.411523 Tz (theorized ) Tj 2.858333 0 Td 46.990741 Tz (that ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1042.915212 Tm 6.358333 0 Td 51.851852 Tz (incidence ) Tj 3.033333 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 50.411523 Tz (autotaxin ) Tj 2.975 0 Td 44.965278 Tz (activity ) Tj 2.411111 0 Td 51.311728 Tz (within ) Tj 2.119444 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 66.111111 Tz (human ) Tj 2.255556 0 Td 52.5 Tz (body, ) Tj 1.847222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1004.206388 Tm 6.358333 0 Td 49.074074 Tz (greater ) Tj 2.236111 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 70.216049 Tz (LPA ) Tj 1.458333 0 Td 48.905724 Tz (generation. ) Tj 3.422222 0 Td 84.259259 Tz (A ) Tj 0.7 0 Td 50.411523 Tz (reduction ) Tj 2.936111 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 960.989899 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.722222 0 Td 45.910494 Tz (capabilities ) Tj 3.558333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 50.05144 Tz (autotaxin ) Tj 2.994444 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 51.388889 Tz (convert ) Tj 2.430556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 72.376543 Tz (LPC ) Tj 1.594444 0 Td 74.537037 Tz (mol ) Tj 51.428571 0 0 51.428571 0 920.050292 Tm 6.358333 0 Td 51.203704 Tz (ecule ) Tj 1.652778 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 71.296296 Tz (LPA ) Tj 1.4 0 Td 60.277778 Tz (would ) Tj 1.886111 0 Td 46.866097 Tz (theoretically ) Tj 3.772222 0 Td 55.902778 Tz (permitan ) Tj 2.838889 0 Td 49.421296 Tz (ultimate ) Tj 2.508333 0 Td 50.771605 Tz (reduction ) Tj 51.428571 0 0 51.428571 0 879.356718 Tm 6.358333 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 45.959596 Tz (possibility ) Tj 3.208333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 59.143519 Tz (unwanted ) Tj 2.994444 0 Td 43.75 Tz (cell ) Tj 1.225 0 Td 46.367521 Tz (proliferation ) Tj 3.811111 0 Td 53.703704 Tz (through ) Tj 2.45 0 Td 55.092593 Tz (reduced ) Tj 51.428571 0 0 51.428571 0 838.277247 Tm 6.377778 0 Td 71.296296 Tz (LPA ) Tj 1.477778 0 Td 53.472222 Tz (presence ) Tj 2.722222 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 47.530864 Tz (subjects ) Tj 2.761111 0 Td 52.5 Tz (body. ) Tj 51.428571 0 0 51.428571 0 781.601467 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.263889 0 Td 60.853909 Tz (mechanism ) Tj 3.422222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 50.05144 Tz (autotaxin ) Tj 2.838889 0 Td 55.092593 Tz (interms ) Tj 2.45 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 55.452675 Tz (enzymatic ) Tj 3.130556 0 Td 45.37037 Tz (activity ) Tj 51.428571 0 0 51.428571 0 742.091371 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.090535 Tz (catalysis ) Tj 2.761111 0 Td 43.75 Tz (to ) Tj 0.816667 0 Td 58.333333 Tz (form ) Tj 1.711111 0 Td 70.216049 Tz (LPA ) Tj 1.516667 0 Td 48.148148 Tz (resides ) Tj 2.275 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 37.808642 Tz (its ) Tj 0.933333 0 Td 52.423747 Tz (phosphodiesterase ) Tj 51.428571 0 0 51.428571 0 700.394366 Tm 6.358333 0 Td 45.075758 Tz (capability. ) Tj 3.286111 0 Td 71.296296 Tz (LPA ) Tj 1.536111 0 Td 56.17284 Tz (can ) Tj 1.283333 0 Td 56.712963 Tz (be ) Tj 0.933333 0 Td 52.572016 Tz (generated ) Tj 3.111111 0 Td 56.712963 Tz (from ) Tj 1.652778 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 52.662037 Tz (cleavage ) Tj 2.780556 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 659.037915 Tm 6.358333 0 Td 52.777778 Tz (phosphodiester ) Tj 4.530556 0 Td 57.685185 Tz (bonds ) Tj 1.847222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 60.763889 Tz (LPC, ) Tj 1.633333 0 Td 53.240741 Tz (through ) Tj 2.352778 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 50.231481 Tz (function ) Tj 2.547222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 48.611111 Tz (a ) Tj 0.427778 0 Td 67.24537 Tz (phos ) Tj 51.428571 0 0 51.428571 0 617.235294 Tm 6.358333 0 Td 51.851852 Tz (pholipase ) Tj 2.975 0 Td 63.194444 Tz (enzyme ) Tj 2.45 0 Td 49.907407 Tz (\(note ) Tj 1.711111 0 Td 57.407407 Tz (Formula ) Tj 2.625 0 Td 33.487654 Tz (I\). ) Tj 31.428571 0 0 31.428571 0 499 Tm 22.813636 0 Td 74.242424 Tz (Formula ) Tj 3.372727 0 Td 53.030303 Tz (I ) Tj 37.142857 0 0 37.142857 0 433.625 Tm 16.046154 0 Td 94.230769 Tz (O ) Tj 4.603846 0 Td 96.474359 Tz (OH ) Tj 31.428571 0 0 31.428571 0 225 Tm 21.318182 0 Td 93.686869 Tz (LPC ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 74.537037 Tz (2 ) Tj 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 42.857143 0 0 42.857143 0 2877 Tm 36.47 0 Td 85.555556 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2848 Tm 68.536364 0 Td 111.363636 Tz (OH ) Tj 68.571429 0 0 68.571429 0 2805.528897 Tm 19.089583 0 Td 54.6875 Tz (HO ) Tj 2.114583 0 Td 82.986111 Tz (O-N-N-O ) Tj 4.76875 0 Td 51.041667 Tz (C-H, ) Tj 2.45 0 Td 98.680556 Tz (SN1\\1 ) Tj 78.571429 0 0 78.571429 0 2766 Tm 24.767273 0 Td 82.727273 Tz (1 ) Tj 0.725455 0 Td 38.181818 Tz (\\ ) Tj 31.428571 0 0 31.428571 0 2760 Tm 44.322727 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2729 Tm 54.918182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2706 Tm 64.559091 0 Td 65.151515 Tz (choline ) Tj 31.428571 0 0 31.428571 0 2669 Tm 49.7 0 Td 93.686869 Tz (LPA ) Tj 51.428571 0 0 51.428571 0 2557.038926 Tm 25.316667 0 Td 46.990741 Tz (In ) Tj 1.011111 0 Td 46.616809 Tz (extracellular ) Tj 4.063889 0 Td 42.12963 Tz (fluids, ) Tj 2.216667 0 Td 42.939815 Tz (this ) Tj 1.458333 0 Td 55.092593 Tz (enzymatic ) Tj 3.383333 0 Td 46.8107 Tz (catalysis ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 1.069444 0 Td 71.296296 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 2512.116129 Tm 25.297222 0 Td 57.87037 Tz (removes ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 50.925926 Tz (choline ) Tj 2.372222 0 Td 52.391975 Tz (group, ) Tj 2.177778 0 Td 50 Tz (leaving ) Tj 2.391667 0 Td 59.953704 Tz (LPA, ) Tj 1.711111 0 Td 58.333333 Tz (which ) Tj 2.022222 0 Td 54.012346 Tz (has ) Tj 1.225 0 Td 55.092593 Tz (a ) Tj 0.583333 0 Td 62.654321 Tz (ten ) Tj 51.428571 0 0 51.428571 0 2469.907455 Tm 25.297222 0 Td 57.685185 Tz (dency ) Tj 1.963889 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 49.331276 Tz (stimulate ) Tj 2.916667 0 Td 42.939815 Tz (cell ) Tj 1.283333 0 Td 56.712963 Tz (growth ) Tj 2.313889 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 46.367521 Tz (proliferation ) Tj 3.888889 0 Td 48.611111 Tz (as ) Tj 0.855556 0 Td 51.851852 Tz (well ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 2425.3 Tm 25.297222 0 Td 52.441077 Tz (chemotaxis. ) Tj 3.752778 0 Td 63.194444 Tz (From ) Tj 1.730556 0 Td 41.481481 Tz (this, ) Tj 1.477778 0 Td 32.407407 Tz (it ) Tj 0.583333 0 Td 52.777778 Tz (appears ) Tj 2.45 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 46.990741 Tz (motility ) Tj 2.488889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 59.62963 Tz (tumor ) Tj 51.428571 0 0 51.428571 0 2382.626943 Tm 25.297222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 38.888889 Tz (is ) Tj 0.738889 0 Td 51.131687 Tz (increased ) Tj 3.013889 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 47.962963 Tz (well, ) Tj 1.730556 0 Td 46.8107 Tz (resulting ) Tj 2.780556 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 48.287037 Tz (properties ) Tj 3.188889 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 57.523148 Tz (gene ) Tj 51.428571 0 0 51.428571 0 2336.54933 Tm 25.297222 0 Td 51.527778 Tz (expression ) Tj 3.305556 0 Td 51.311728 Tz (within ) Tj 2.080556 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 55.092593 Tz (carcinomas ) Tj 3.538889 0 Td 51.851852 Tz (\(Such ) Tj 1.75 0 Td 44.290123 Tz (as, ) Tj 1.011111 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 47.170782 Tz (instance, ) Tj 51.428571 0 0 51.428571 0 2294.713043 Tm 25.277778 0 Td 49.151235 Tz (breast ) Tj 1.983333 0 Td 54.012346 Tz (cancer ) Tj 2.138889 0 Td 41.666667 Tz (cells\), ) Tj 2.022222 0 Td 52.314815 Tz (causing ) Tj 2.430556 0 Td 48.148148 Tz (further ) Tj 2.216667 0 Td 51.851852 Tz (processing ) Tj 3.344444 0 Td 46.990741 Tz (into ) Tj 1.380556 0 Td 55.092593 Tz (a ) Tj 0.563889 0 Td 58.333333 Tz (form ) Tj 51.428571 0 0 51.428571 0 2251.184178 Tm 25.277778 0 Td 46.990741 Tz (that ) Tj 1.380556 0 Td 38.888889 Tz (is ) Tj 0.7 0 Td 49.331276 Tz (bioactive ) Tj 2.897222 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 47.43266 Tz (potentially ) Tj 3.402778 0 Td 52.175926 Tz (dangerous. ) Tj 3.422222 0 Td 50.555556 Tz (Metastasis ) Tj 3.305556 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 2208.993412 Tm 25.297222 0 Td 53.619529 Tz (oncogenesis ) Tj 3.869444 0 Td 58.333333 Tz (of ) Tj 0.933333 0 Td 52.391975 Tz (cancer ) Tj 2.197222 0 Td 44.074074 Tz (cells ) Tj 1.613889 0 Td 55.092593 Tz (appear ) Tj 2.275 0 Td 43.75 Tz (to ) Tj 0.875 0 Td 55.092593 Tz (occur ) Tj 1.925 0 Td 50.231481 Tz (as ) Tj 0.913889 0 Td 51.851852 Tz (well ) Tj 1.575 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 2168.536618 Tm 25.297222 0 Td 49.826389 Tz (elevated ) Tj 2.761111 0 Td 45.37037 Tz (levels ) Tj 2.002778 0 Td 59.953704 Tz (of ) Tj 1.011111 0 Td 70.216049 Tz (LPA ) Tj 1.594444 0 Td 50.925926 Tz (present ) Tj 2.508333 0 Td 50.771605 Tz (within ) Tj 2.197222 0 Td 51.851852 Tz (a ) Tj 0.680556 0 Td 48.611111 Tz (targeted ) Tj 2.702778 0 Td 47.222222 Tz (region. ) Tj 51.428571 0 0 51.428571 0 2124.55122 Tm 25.316667 0 Td 51.49177 Tz (Increased ) Tj 2.916667 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 51.527778 Tz (expression ) Tj 3.286111 0 Td 52.932099 Tz (has ) Tj 1.147222 0 Td 56.712963 Tz (been ) Tj 1.575 0 Td 45.694444 Tz (identified ) Tj 2.916667 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 46.666667 Tz (renal ) Tj 1.594444 0 Td 55.740741 Tz (carci ) Tj 51.428571 0 0 51.428571 0 2084.269368 Tm 25.297222 0 Td 59.62963 Tz (noma, ) Tj 2.002778 0 Td 48.611111 Tz (metastatic ) Tj 3.091667 0 Td 48.611111 Tz (breast ) Tj 1.925 0 Td 48.611111 Tz (cancer, ) Tj 2.236111 0 Td 50 Tz (thyroid ) Tj 2.294444 0 Td 53.148148 Tz (carcinoma, ) Tj 3.422222 0 Td 60.185185 Tz (Hodgkin ) Tj 51.428571 0 0 51.428571 0 2044.067416 Tm 25.297222 0 Td 60.493827 Tz (lymphoma, ) Tj 3.480556 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 49.016204 Tz (invasive ) Tj 2.527778 0 Td 52.391975 Tz (glioblastoma ) Tj 3.966667 0 Td 51.557239 Tz (multiforme. ) Tj 51.428571 0 0 51.428571 0 2001.230179 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.563889 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 50.231481 Tz (thus ) Tj 1.361111 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 54.444444 Tz (determined ) Tj 3.402778 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 44.907407 Tz (ability ) Tj 2.022222 0 Td 46.990741 Tz (to ) Tj 0.7 0 Td 49.016204 Tz (prevent, ) Tj 2.488889 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 45.37037 Tz (at ) Tj 51.428571 0 0 51.428571 0 1957.711538 Tm 25.297222 0 Td 44.722222 Tz (least ) Tj 1.497222 0 Td 49.074074 Tz (reduce, ) Tj 2.216667 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 61.574074 Tz (amount ) Tj 2.333333 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 71.296296 Tz (LPA ) Tj 1.438889 0 Td 50.771605 Tz (within ) Tj 1.963889 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 66.111111 Tz (human ) Tj 2.138889 0 Td 59.953704 Tz (body ) Tj 1.575 0 Td 52.5 Tz (holds ) Tj 51.428571 0 0 51.428571 0 1920.089987 Tm 25.297222 0 Td 47.962963 Tz (great ) Tj 1.711111 0 Td 56.018519 Tz (promise ) Tj 2.625 0 Td 38.888889 Tz (at, ) Tj 0.991667 0 Td 47.170782 Tz (likewise, ) Tj 2.838889 0 Td 50.05144 Tz (reducing, ) Tj 2.994444 0 Td 42.12963 Tz (if ) Tj 0.719444 0 Td 50.771605 Tz (not ) Tj 1.147222 0 Td 49.494949 Tz (preventing, ) Tj 3.538889 0 Td 50.771605 Tz (the ) Tj 48.571429 0 0 48.571429 0 1876 Tm 26.785294 0 Td 54.901961 Tz (onset ) Tj 1.770588 0 Td 56.617647 Tz (of ) Tj 0.761765 0 Td 49.509804 Tz (certain ) Tj 2.223529 0 Td 51.041667 Tz (cancers. ) Tj 2.635294 0 Td 37.745098 Tz (It ) Tj 0.555882 0 Td 57.189542 Tz (has ) Tj 1.152941 0 Td 61.764706 Tz (been ) Tj 1.585294 0 Td 53.186275 Tz (theorized,as ) Tj 3.973529 0 Td 56.960784 Tz (noted ) Tj 1.832353 0 Td 54.901961 Tz (above, ) Tj 51.428571 0 0 51.428571 0 1833.622378 Tm 25.277778 0 Td 46.990741 Tz (that ) Tj 1.205556 0 Td 50.05144 Tz (autotaxin ) Tj 2.858333 0 Td 50.356125 Tz (modifications ) Tj 4.063889 0 Td 68.055556 Tz (may ) Tj 1.341667 0 Td 51.388889 Tz (prevent ) Tj 2.236111 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 50.673401 Tz (undesirable ) Tj 3.461111 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1794.807169 Tm 25.297222 0 Td 50.925926 Tz (version ) Tj 2.313889 0 Td 57.523148 Tz (from ) Tj 1.594444 0 Td 73.45679 Tz (LPC ) Tj 1.516667 0 Td 43.75 Tz (to ) Tj 0.758333 0 Td 59.953704 Tz (LPA; ) Tj 1.652778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 43.981481 Tz (ability ) Tj 2.061111 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 48.206019 Tz (actually ) Tj 2.508333 0 Td 55.416667 Tz (accomplish ) Tj 51.428571 0 0 51.428571 0 1749.977778 Tm 25.316667 0 Td 54.282407 Tz (Such ) Tj 1.458333 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 45.37037 Tz (result ) Tj 1.769444 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 56.712963 Tz (been ) Tj 1.536111 0 Td 46.180556 Tz (elusive, ) Tj 2.391667 0 Td 54.282407 Tz (however, ) Tj 2.741667 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 53.472222 Tz (degree ) Tj 51.428571 0 0 51.428571 0 1709.520315 Tm 25.297222 0 Td 52.211934 Tz (necessary ) Tj 3.227778 0 Td 48.611111 Tz (for ) Tj 1.225 0 Td 46.450617 Tz (effective ) Tj 2.897222 0 Td 50.673401 Tz (broad-scale ) Tj 3.752778 0 Td 44.191919 Tz (utilization ) Tj 3.325 0 Td 59.953704 Tz (of ) Tj 0.991667 0 Td 55.092593 Tz (such ) Tj 1.730556 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1667.55092 Tm 25.297222 0 Td 55.555556 Tz (method. ) Tj 2.547222 0 Td 66.975309 Tz (Any ) Tj 1.458333 0 Td 50.501543 Tz (modification ) Tj 3.85 0 Td 51.388889 Tz (thereof ) Tj 2.294444 0 Td 58.333333 Tz (must ) Tj 1.575 0 Td 48.148148 Tz (exhibit ) Tj 2.216667 0 Td 56.712963 Tz (an ) Tj 0.875 0 Td 44.444444 Tz (ability ) Tj 2.080556 0 Td 45.37037 Tz (to ) Tj 52.857143 0 0 52.857143 0 1626.530249 Tm 24.613514 0 Td 44.717445 Tz (drastically ) Tj 3.140541 0 Td 51.501502 Tz (reduce ) Tj 1.967568 0 Td 49.399399 Tz (the ) Tj 1.002703 0 Td 44.932432 Tz (activity ) Tj 2.27027 0 Td 55.18018 Tz (of ) Tj 0.737838 0 Td 48.698699 Tz (autotaxin ) Tj 2.781081 0 Td 52.342342 Tz (while ) Tj 1.721622 0 Td 43.513514 Tz (also, ) Tj 1.437838 0 Td 53.603604 Tz (prefer ) Tj 51.428571 0 0 51.428571 0 1587.797297 Tm 25.297222 0 Td 51.851852 Tz (ably ) Tj 1.438889 0 Td 48.935185 Tz (exhibiting ) Tj 3.091667 0 Td 47.800926 Tz (oral ) Tj 1.341667 0 Td 46.234568 Tz (bioavailability ) Tj 4.336111 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 47.314815 Tz (well. ) Tj 40 0 0 40 0 1548 Tm 33.475 0 Td 64.583333 Tz (Past ) Tj 1.975 0 Td 81.25 Tz (work ) Tj 2.375 0 Td 58.333333 Tz (at ) Tj 1.1 0 Td 100 Tz (ATX ) Tj 2.275 0 Td 60 Tz (inhibition ) Tj 4.075 0 Td 68.055556 Tz (has ) Tj 1.7 0 Td 67.1875 Tz (included ) Tj 3.7 0 Td 59.375 Tz (L-histidine. ) Tj 51.428571 0 0 51.428571 0 1502.265306 Tm 25.297222 0 Td 50 Tz (Unfortunately, ) Tj 4.491667 0 Td 51.203704 Tz (millimolar ) Tj 3.286111 0 Td 50.462963 Tz (concentrations ) Tj 4.511111 0 Td 59.143519 Tz (were ) Tj 1.691667 0 Td 50.231481 Tz (required ) Tj 2.663889 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 1460.540173 Tm 25.297222 0 Td 57.253086 Tz (any ) Tj 1.244444 0 Td 44.650206 Tz (efficacy, ) Tj 2.605556 0 Td 51.851852 Tz (and, ) Tj 1.516667 0 Td 60.763889 Tz (more ) Tj 1.672222 0 Td 48.881173 Tz (importantly, ) Tj 3.772222 0 Td 49.421296 Tz (Zinc ) Tj 1.4 0 Td 46.296296 Tz (sulfate ) Tj 2.158333 0 Td 46.990741 Tz (reversal ) Tj 2.508333 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 1416.459057 Tm 25.277778 0 Td 43.75 Tz (this ) Tj 1.380556 0 Td 45.37037 Tz (effect ) Tj 1.944444 0 Td 44.290123 Tz (\(in ) Tj 1.108333 0 Td 52.849003 Tz (Submillimolar ) Tj 4.394444 0 Td 49.691358 Tz (concentrations\) ) Tj 4.802778 0 Td 52.932099 Tz (suggested ) Tj 3.15 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 1375.453608 Tm 25.297222 0 Td 46.990741 Tz (inhibition ) Tj 3.227778 0 Td 60.493827 Tz (mechanism ) Tj 3.655556 0 Td 50.771605 Tz (involving ) Tj 3.130556 0 Td 46.548822 Tz (interaction ) Tj 3.480556 0 Td 51.851852 Tz (with ) Tj 1.633333 0 Td 49.691358 Tz (the ) Tj 1.263889 0 Td 58.333333 Tz (two ) Tj 51.428571 0 0 51.428571 0 1333.350384 Tm 25.297222 0 Td 48.611111 Tz (native ) Tj 2.022222 0 Td 48.070988 Tz (active ) Tj 2.022222 0 Td 42.12963 Tz (site ) Tj 1.341667 0 Td 52.5 Tz (metal ) Tj 1.866667 0 Td 51.041667 Tz (ions ) Tj 1.516667 0 Td 46.585648 Tz (thereof. ) Tj 2.527778 0 Td 56.388889 Tz (Other ) Tj 1.925 0 Td 47.530864 Tz (potential ) Tj 2.819444 0 Td 78.858025 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1294.655969 Tm 25.297222 0 Td 46.018519 Tz (inhibitors ) Tj 3.188889 0 Td 56.712963 Tz (have ) Tj 1.788889 0 Td 51.851852 Tz (included ) Tj 2.897222 0 Td 49.691358 Tz (the ) Tj 1.283333 0 Td 52.256944 Tz (products ) Tj 2.916667 0 Td 59.953704 Tz (of ) Tj 0.991667 0 Td 56.588319 Tz (ATX-catalyzed ) Tj 51.428571 0 0 51.428571 0 1254.612221 Tm 25.277778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.208333 0 Td 55.092593 Tz (of ) Tj 0.777778 0 Td 72.376543 Tz (LPC ) Tj 1.458333 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 52.175926 Tz (sphingosyl ) Tj 3.266667 0 Td 53.376906 Tz (phosphorylcholine ) Tj 5.6 0 Td 53.472222 Tz (\(SPC\), ) Tj 51.428571 0 0 51.428571 0 1210.242424 Tm 25.297222 0 Td 60.763889 Tz (LPA, ) Tj 1.691667 0 Td 60.493827 Tz (and ) Tj 1.302778 0 Td 66.975309 Tz (S1P ) Tj 1.516667 0 Td 46.118234 Tz (respectively. ) Tj 3.869444 0 Td 47.638889 Tz (Inhibition ) Tj 3.091667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 59.953704 Tz (by ) Tj 0.991667 0 Td 72.376543 Tz (LPA ) Tj 1.497222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1168.842353 Tm 25.316667 0 Td 64.814815 Tz (S1P ) Tj 1.302778 0 Td 50.231481 Tz (suggests ) Tj 2.566667 0 Td 45.37037 Tz (that ) Tj 1.186111 0 Td 53.703704 Tz (product ) Tj 2.372222 0 Td 54.6875 Tz (feedback ) Tj 2.761111 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 66.975309 Tz (may ) Tj 1.341667 0 Td 49.259259 Tz (contribute ) Tj 51.428571 0 0 51.428571 0 1126.761062 Tm 25.277778 0 Td 45.37037 Tz (to ) Tj 0.875 0 Td 48.287037 Tz (regulation ) Tj 3.169444 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 49.826389 Tz (function ) Tj 2.683333 0 Td 43.75 Tz (in ) Tj 0.816667 0 Td 46.666667 Tz (vivo. ) Tj 1.633333 0 Td 51.527778 Tz (Additional ) Tj 3.402778 0 Td 50.231481 Tz (reported ) Tj 48.571429 0 0 48.571429 0 1085 Tm 26.785294 0 Td 83.496732 Tz (ATX ) Tj 1.832353 0 Td 49.068627 Tz (inhibitors ) Tj 3.294118 0 Td 54.215686 Tz (share ) Tj 1.955882 0 Td 50.980392 Tz (several ) Tj 2.491176 0 Td 74.918301 Tz (common ) Tj 3.067647 0 Td 48.039216 Tz (structural ) Tj 3.232353 0 Td 48.039216 Tz (features, ) Tj 51.428571 0 0 51.428571 0 1047.743802 Tm 25.297222 0 Td 51.49177 Tz (including ) Tj 2.936111 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 51.851852 Tz (phosphate, ) Tj 3.286111 0 Td 50.925926 Tz (thiophosphate, ) Tj 4.472222 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 56.271044 Tz (phosphonate ) Tj 3.888889 0 Td 67.24537 Tz (head ) Tj 51.428571 0 0 51.428571 0 1001.708223 Tm 25.297222 0 Td 56.388889 Tz (group ) Tj 1.983333 0 Td 50.636574 Tz (attached ) Tj 2.702778 0 Td 46.990741 Tz (either ) Tj 1.944444 0 Td 53.472222 Tz (with ) Tj 1.555556 0 Td 55.092593 Tz (or ) Tj 0.913889 0 Td 52.777778 Tz (without ) Tj 2.508333 0 Td 51.851852 Tz (a ) Tj 0.622222 0 Td 47.530864 Tz (linker ) Tj 1.963889 0 Td 45.37037 Tz (to ) Tj 0.836111 0 Td 56.712963 Tz (an ) Tj 0.991667 0 Td 47.962963 Tz (alkyl ) Tj 51.428571 0 0 51.428571 0 959.666222 Tm 25.297222 0 Td 48.611111 Tz (chain, ) Tj 2.041667 0 Td 59.62963 Tz (which ) Tj 2.061111 0 Td 55.092593 Tz (can ) Tj 1.322222 0 Td 51.851852 Tz (vary ) Tj 1.536111 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 47.222222 Tz (overall ) Tj 2.294444 0 Td 49.691358 Tz (length ) Tj 2.1 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 56.17284 Tz (can ) Tj 1.302778 0 Td 58.333333 Tz (be ) Tj 0.972222 0 Td 46.990741 Tz (either ) Tj 51.428571 0 0 51.428571 0 918.711443 Tm 25.316667 0 Td 48.251029 Tz (saturated ) Tj 2.916667 0 Td 51.851852 Tz (or ) Tj 0.894444 0 Td 48.611111 Tz (unsaturated. ) Tj 3.888889 0 Td 56.30787 Tz (However, ) Tj 2.994444 0 Td 51.203704 Tz (these ) Tj 1.808333 0 Td 61.934156 Tz (compounds ) Tj 3.636111 0 Td 55.092593 Tz (both ) Tj 51.428571 0 0 51.428571 0 877.64142 Tm 25.297222 0 Td 51.851852 Tz (lack ) Tj 1.341667 0 Td 46.843434 Tz (substantial ) Tj 3.208333 0 Td 45.694444 Tz (structural ) Tj 2.877778 0 Td 46.090535 Tz (diversity ) Tj 2.625 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 39.699074 Tz (fail ) Tj 1.088889 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 57.523148 Tz (meet ) Tj 1.497222 0 Td 48.935185 Tz (Lipinski's ) Tj 51.428571 0 0 51.428571 0 835.216282 Tm 25.297222 0 Td 50.771605 Tz (empirical ) Tj 2.994444 0 Td 46.018519 Tz (rules ) Tj 1.633333 0 Td 44.560185 Tz (that ) Tj 1.283333 0 Td 48.611111 Tz (characterize ) Tj 3.713889 0 Td 73.45679 Tz (90% ) Tj 1.555556 0 Td 61.574074 Tz (of ) Tj 0.816667 0 Td 46.990741 Tz (orally ) Tj 1.925 0 Td 49.421296 Tz (bioavailable ) Tj 51.428571 0 0 51.428571 0 798.059355 Tm 25.297222 0 Td 49.151235 Tz (drugs. ) Tj 2.080556 0 Td 34.027778 Tz (It ) Tj 0.680556 0 Td 38.888889 Tz (is ) Tj 0.758333 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 49.259259 Tz (great ) Tj 1.730556 0 Td 54.444444 Tz (importance ) Tj 3.5 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 46.990741 Tz (identify ) Tj 2.566667 0 Td 51.203704 Tz (novel ) Tj 1.847222 0 Td 48.971193 Tz (non-lipid ) Tj 51.428571 0 0 51.428571 0 752.593789 Tm 25.316667 0 Td 45.37037 Tz (structural ) Tj 2.955556 0 Td 48.148148 Tz (classes ) Tj 2.255556 0 Td 53.703704 Tz (capable ) Tj 2.488889 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 46.990741 Tz (inhibiting ) Tj 3.033333 0 Td 76.697531 Tz (ATX ) Tj 1.613889 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 58.333333 Tz (which ) Tj 2.002778 0 Td 50.771605 Tz (are ) Tj 51.428571 0 0 51.428571 0 709.828571 Tm 25.297222 0 Td 46.990741 Tz (orally ) Tj 1.847222 0 Td 48.881173 Tz (bioavailable ) Tj 3.655556 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 43.425926 Tz (treat ) Tj 1.419444 0 Td 46.759259 Tz (certain ) Tj 2.119444 0 Td 58.981481 Tz (tumor ) Tj 1.866667 0 Td 45.775463 Tz (classes. ) Tj 2.333333 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 53.472222 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 668.536082 Tm 25.277778 0 Td 46.180556 Tz (tors ) Tj 1.438889 0 Td 48.935185 Tz (consistent ) Tj 3.247222 0 Td 53.472222 Tz (with ) Tj 1.672222 0 Td 48.287037 Tz (Lipinski's ) Tj 3.266667 0 Td 46.666667 Tz (rules ) Tj 1.711111 0 Td 56.712963 Tz (have ) Tj 1.691667 0 Td 56.712963 Tz (been ) Tj 1.730556 0 Td 45.694444 Tz (identified ) Tj 51.428571 0 0 51.428571 0 628.269091 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.808333 0 Td 56.271044 Tz (model-based ) Tj 3.888889 0 Td 45.694444 Tz (structural ) Tj 2.955556 0 Td 49.259259 Tz (Screening, ) Tj 3.15 0 Td 55.092593 Tz (such ) Tj 1.516667 0 Td 50.231481 Tz (as ) Tj 0.816667 0 Td 51.311728 Tz (within ) Tj 2.061111 0 Td 52.662037 Tz (U.S. ) Tj 51.428571 0 0 51.428571 0 585.638889 Tm 25.297222 0 Td 49.789562 Tz (Provisional ) Tj 3.441667 0 Td 50.771605 Tz (Patent ) Tj 1.905556 0 Td 52.146465 Tz (Application ) Tj 3.597222 0 Td 52.441077 Tz (61/002,687, ) Tj 3.616667 0 Td 45.37037 Tz (entitled ) Tj 2.313889 0 Td 62.037037 Tz (Method ) Tj 51.428571 0 0 51.428571 0 543.710214 Tm 25.297222 0 Td 49.691358 Tz (for ) Tj 1.011111 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 45.833333 Tz (Identification ) Tj 4.005556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 64.814815 Tz (Compounds ) Tj 3.655556 0 Td 62.384259 Tz (Used ) Tj 1.652778 0 Td 42.12963 Tz (in ) Tj 0.680556 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 55.452675 Tz (Treatment ) Tj 3.111111 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 501.839566 Tm 25.297222 0 Td 50.462963 Tz (Certain ) Tj 2.313889 0 Td 53.703704 Tz (Tumors. ) Tj 2.508333 0 Td 56.388889 Tz (Using ) Tj 1.886111 0 Td 53.652263 Tz (Autotaxin ) Tj 3.130556 0 Td 46.342593 Tz (Inhibitors ) Tj 3.013889 0 Td 48.611111 Tz (as ) Tj 0.816667 0 Td 63.194444 Tz (Chemothera ) Tj 51.428571 0 0 51.428571 0 463.571429 Tm 25.297222 0 Td 49.151235 Tz (peutic ) Tj 1.905556 0 Td 64.814815 Tz (Compounds ) Tj 3.636111 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 63.194444 Tz (Method ) Tj 2.411111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 50.636574 Tz (Treating ) Tj 2.527778 0 Td 61.033951 Tz (Tumors ) Tj 2.372222 0 Td 57.037037 Tz (Using ) Tj 51.428571 0 0 51.428571 0 421.30596 Tm 25.297222 0 Td 59.62963 Tz (Those ) Tj 2.022222 0 Td 60.925926 Tz (Compounds, ) Tj 4.238889 0 Td 43.425926 Tz (filed ) Tj 1.555556 0 Td 58.333333 Tz (on ) Tj 0.972222 0 Td 56.712963 Tz (Nov. ) Tj 1.711111 0 Td 45.37037 Tz (13, ) Tj 1.108333 0 Td 53.148148 Tz (2007, ) Tj 1.886111 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 59.953704 Tz (by ) Tj 0.972222 0 Td 56.388889 Tz (large ) Tj 51.428571 0 0 51.428571 0 380 Tm 25.316667 0 Td 47.962963 Tz (scale ) Tj 1.652778 0 Td 51.49177 Tz (Screening ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 43.930041 Tz (libraries ) Tj 2.586111 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 52.614379 Tz (phosphodiesterase ) Tj 5.522222 0 Td 60.493827 Tz (and ) Tj 1.283333 0 Td 51.851852 Tz (kinase ) Tj 40 0 0 40 0 343 Tm 32.525 0 Td 57.19697 Tz (inhibitors. ) Tj 51.428571 0 0 51.428571 0 296.564661 Tm 26.036111 0 Td 37.268519 Tz (It ) Tj 0.641667 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 48.971193 Tz (believed, ) Tj 2.838889 0 Td 53.240741 Tz (without ) Tj 2.411111 0 Td 49.537037 Tz (relying ) Tj 2.255556 0 Td 59.953704 Tz (upon ) Tj 1.633333 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 45.775463 Tz (specific ) Tj 2.411111 0 Td 43.75 Tz (scientific ) Tj 51.428571 0 0 51.428571 0 253.445798 Tm 25.277778 0 Td 45.37037 Tz (basis, ) Tj 1.827778 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 51.851852 Tz (lack ) Tj 1.380556 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 46.090535 Tz (diversity ) Tj 2.663889 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 49.826389 Tz (reported ) Tj 2.488889 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 44.781145 Tz (inhibitors, ) Tj 3.111111 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 210.722444 Tm 25.297222 0 Td 53.796296 Tz (noted ) Tj 1.886111 0 Td 52.391975 Tz (above, ) Tj 2.158333 0 Td 38.888889 Tz (is ) Tj 0.758333 0 Td 50.231481 Tz (due, ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.797222 0 Td 44.074074 Tz (part, ) Tj 1.575 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 51.851852 Tz (lack ) Tj 1.497222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 58.333333 Tz (a ) Tj 0.602778 0 Td 49.85755 Tz (characterized ) Tj 51.428571 0 0 51.428571 0 169.342355 Tm 25.277778 0 Td 51.66122 Tz (three-dimensional ) Tj 5.813889 0 Td 47.170782 Tz (structure ) Tj 3.072222 0 Td 59.953704 Tz (of ) Tj 1.166667 0 Td 48.611111 Tz (the ) Tj 1.419444 0 Td 57.407407 Tz (enzyme. ) Tj 2.975 0 Td 62.654321 Tz (The ) Tj 1.613889 0 Td 78.858025 Tz (ATX ) Tj ET Q endstream endobj 192 0 obj << /Length 1 >> stream q endstream endobj 193 0 obj << /Length 50042 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,343.934 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.454054 0 Td 72.522523 Tz (3 ) Tj 51.428571 0 0 51.428571 0 2914.436435 Tm 6.377778 0 Td 55.497685 Tz (sequence ) Tj 2.955556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 55.092593 Tz (over ) Tj 1.575 0 Td 62.654321 Tz (860 ) Tj 1.4 0 Td 59.62963 Tz (amino ) Tj 2.119444 0 Td 49.259259 Tz (acids ) Tj 1.788889 0 Td 38.888889 Tz (is ) Tj 0.777778 0 Td 51.851852 Tz (divided ) Tj 2.488889 0 Td 46.180556 Tz (into ) Tj 1.438889 0 Td 47.685185 Tz (several ) Tj 51.428571 0 0 51.428571 0 2874.093023 Tm 6.358333 0 Td 55.092593 Tz (domains, ) Tj 2.877778 0 Td 50.771605 Tz (including ) Tj 2.975 0 Td 51.851852 Tz (a ) Tj 0.563889 0 Td 46.296296 Tz (central ) Tj 2.177778 0 Td 45.37037 Tz (catalytic ) Tj 2.683333 0 Td 60.493827 Tz (domain ) Tj 2.430556 0 Td 61.168981 Tz (composed ) Tj 3.169444 0 Td 56.712963 Tz (of ) Tj 40 0 0 40 0 2834 Tm 8.175 0 Td 70 Tz (about ) Tj 2.325 0 Td 81.944444 Tz (400 ) Tj 1.725 0 Td 76.666667 Tz (amino ) Tj 2.6 0 Td 59.027778 Tz (acids. ) Tj 2.425 0 Td 97.222222 Tz (ATX ) Tj 2.075 0 Td 50 Tz (is ) Tj 0.9 0 Td 70.833333 Tz (a ) Tj 0.725 0 Td 85.416667 Tz (member ) Tj 3.3 0 Td 75 Tz (of ) Tj 1.1 0 Td 62.5 Tz (the ) Tj 1.4 0 Td 65 Tz (nucleotide ) Tj 51.428571 0 0 51.428571 0 2787.951106 Tm 6.358333 0 Td 52.637486 Tz (pyrophosphatase/phosphodiesterase ) Tj 10.577778 0 Td 60.277778 Tz (\(NPP\) ) Tj 1.983333 0 Td 47.685185 Tz (family, ) Tj 2.119444 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 51.041667 Tz (well ) Tj 1.380556 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 2744.681293 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (alkaline ) Tj 2.45 0 Td 53.914141 Tz (phosphatase ) Tj 3.694444 0 Td 49.421296 Tz (Superfamily. ) Tj 3.694444 0 Td 50.434028 Tz (Crystallographic ) Tj 4.997222 0 Td 54.444444 Tz (struc ) Tj 51.428571 0 0 51.428571 0 2698.482467 Tm 6.338889 0 Td 47.314815 Tz (tures ) Tj 1.691667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 48.148148 Tz (several ) Tj 2.275 0 Td 48.206019 Tz (alkaline ) Tj 2.527778 0 Td 54.208754 Tz (phosphatase ) Tj 3.830556 0 Td 51.851852 Tz (Superfamily ) Tj 3.694444 0 Td 62.962963 Tz (members ) Tj 51.428571 0 0 51.428571 0 2652.019305 Tm 6.338889 0 Td 57.523148 Tz (have ) Tj 1.691667 0 Td 56.712963 Tz (been ) Tj 1.711111 0 Td 48.251029 Tz (available ) Tj 2.955556 0 Td 46.450617 Tz (for ) Tj 1.166667 0 Td 51.041667 Tz (decades. ) Tj 2.8 0 Td 57.685185 Tz (These ) Tj 2.061111 0 Td 45.833333 Tz (crystal ) Tj 2.275 0 Td 46.990741 Tz (structures ) Tj 40 0 0 40 0 2616 Tm 8.2 0 Td 77.083333 Tz (show ) Tj 2.175 0 Td 70 Tz (remarkable ) Tj 4.4 0 Td 58.75 Tz (structural ) Tj 3.775 0 Td 65.625 Tz (conservation ) Tj 5 0 Td 56.25 Tz (in ) Tj 0.925 0 Td 66.666667 Tz (a ) Tj 0.675 0 Td 65.833333 Tz (small ) Tj 2.225 0 Td 65.625 Tz (core ) Tj 1.85 0 Td 77.777778 Tz (Sur ) Tj 51.428571 0 0 51.428571 0 2568.78961 Tm 6.358333 0 Td 54.6875 Tz (rounding ) Tj 2.975 0 Td 49.691358 Tz (the ) Tj 1.263889 0 Td 45.010288 Tz (catalytic ) Tj 2.8 0 Td 39.537037 Tz (site, ) Tj 1.516667 0 Td 52.932099 Tz (but ) Tj 1.283333 0 Td 50.106838 Tz (unfortunately ) Tj 4.258333 0 Td 61.574074 Tz (show ) Tj 1.866667 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 2521.004926 Tm 6.358333 0 Td 47.222222 Tz (pletely ) Tj 2.275 0 Td 46.090535 Tz (different ) Tj 2.741667 0 Td 45.694444 Tz (structural ) Tj 3.013889 0 Td 46.234568 Tz (characteristics ) Tj 4.433333 0 Td 50.462963 Tz (outside ) Tj 2.411111 0 Td 42.12963 Tz (this ) Tj 1.302778 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 2481.587413 Tm 6.377778 0 Td 51.851852 Tz (served ) Tj 1.983333 0 Td 46.666667 Tz (core. ) Tj 1.555556 0 Td 57.928241 Tz (Sequence ) Tj 2.877778 0 Td 61.168981 Tz (homology ) Tj 3.091667 0 Td 51.851852 Tz (of ) Tj 0.680556 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 48.611111 Tz (alkaline ) Tj 2.411111 0 Td 53.472222 Tz (phosphatases ) Tj 40 0 0 40 0 2441 Tm 8.15 0 Td 69.791667 Tz (with ) Tj 1.9 0 Td 100 Tz (ATX ) Tj 2.1 0 Td 69.791667 Tz (does ) Tj 1.95 0 Td 66.666667 Tz (not ) Tj 1.4 0 Td 72.916667 Tz (exceed ) Tj 2.975 0 Td 87.5 Tz (14% ) Tj 1.85 0 Td 76.388889 Tz (and ) Tj 1.625 0 Td 50 Tz (is ) Tj 0.875 0 Td 62.5 Tz (therefore ) Tj 3.65 0 Td 57.986111 Tz (insufficient ) Tj 51.428571 0 0 51.428571 0 2394.692924 Tm 6.358333 0 Td 48.611111 Tz (for ) Tj 1.166667 0 Td 51.203704 Tz (generation ) Tj 3.422222 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 58.333333 Tz (a ) Tj 0.661111 0 Td 53.472222 Tz (high ) Tj 1.633333 0 Td 47.685185 Tz (quality ) Tj 2.333333 0 Td 61.168981 Tz (homology ) Tj 3.325 0 Td 58.981481 Tz (model ) Tj 2.119444 0 Td 43.75 Tz (in ) Tj 0.855556 0 Td 59.41358 Tz (any ) Tj 51.428571 0 0 51.428571 0 2350.540284 Tm 6.358333 0 Td 50.771605 Tz (region ) Tj 1.983333 0 Td 50.462963 Tz (outside ) Tj 2.255556 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 53.596866 Tz (approximately ) Tj 4.394444 0 Td 58.333333 Tz (100 ) Tj 1.186111 0 Td 59.62963 Tz (amino ) Tj 1.925 0 Td 51.851852 Tz (acid ) Tj 1.4 0 Td 45.910494 Tz (structurally ) Tj 51.428571 0 0 51.428571 0 2303.88 Tm 6.358333 0 Td 54.73251 Tz (conserved ) Tj 3.130556 0 Td 47.962963 Tz (core. ) Tj 1.652778 0 Td 63.734568 Tz (The ) Tj 1.361111 0 Td 49.151235 Tz (recent ) Tj 2.002778 0 Td 47.530864 Tz (report ) Tj 1.925 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 46.296296 Tz (crystal ) Tj 2.158333 0 Td 47.170782 Tz (structure ) Tj 2.761111 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 2261.423123 Tm 6.338889 0 Td 47.170782 Tz (bacterial ) Tj 2.663889 0 Td 74.537037 Tz (NPP ) Tj 1.458333 0 Td 63.194444 Tz (enzyme ) Tj 2.391667 0 Td 54.282407 Tz (with ) Tj 1.438889 0 Td 73.45679 Tz (30% ) Tj 1.477778 0 Td 46.585648 Tz (identity ) Tj 2.372222 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 0.991667 0 Td 76.697531 Tz (ATX ) Tj 1.516667 0 Td 45.730453 Tz (catalytic ) Tj 51.428571 0 0 51.428571 0 2216.813459 Tm 6.358333 0 Td 52.662037 Tz (core ) Tj 1.361111 0 Td 60.493827 Tz (domain ) Tj 2.313889 0 Td 53.240741 Tz (enabled ) Tj 2.372222 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 56.565657 Tz (development ) Tj 3.830556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 45.046296 Tz (structural ) Tj 2.877778 0 Td 59.62963 Tz (model ) Tj 1.905556 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2173.666667 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 45.37037 Tz (catalytic ) Tj 2.644444 0 Td 59.953704 Tz (domain ) Tj 2.333333 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 55.092593 Tz (prove ) Tj 1.827778 0 Td 48.611111 Tz (useful ) Tj 1.944444 0 Td 43.75 Tz (in ) Tj 0.7 0 Td 51.49177 Tz (structure ) Tj 51.428571 0 0 51.428571 0 2133.368113 Tm 6.338889 0 Td 56.388889 Tz (based ) Tj 1.808333 0 Td 55.902778 Tz (drug ) Tj 1.477778 0 Td 49.074074 Tz (design. ) Tj 2.177778 0 Td 57.118056 Tz (Although ) Tj 2.858333 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 45.959596 Tz (significant ) Tj 3.169444 0 Td 55.902778 Tz (improvement, ) Tj 4.180556 0 Td 55.902778 Tz (Such ) Tj 51.428571 0 0 51.428571 0 2087.915094 Tm 6.358333 0 Td 55.092593 Tz (a ) Tj 0.427778 0 Td 61.574074 Tz (homology ) Tj 3.111111 0 Td 59.62963 Tz (model ) Tj 1.925 0 Td 59.143519 Tz (must ) Tj 1.516667 0 Td 58.333333 Tz (be ) Tj 0.797222 0 Td 51.388889 Tz (applied ) Tj 2.294444 0 Td 49.259259 Tz (cautiously ) Tj 3.091667 0 Td 48.611111 Tz (as ) Tj 0.719444 0 Td 54.503367 Tz (involvement ) Tj 51.428571 0 0 51.428571 0 2041.184116 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 52.932099 Tz (the ) Tj 1.127778 0 Td 49.583333 Tz (c-terminal ) Tj 3.208333 0 Td 48.860399 Tz (nuclease-like ) Tj 4.005556 0 Td 59.953704 Tz (domain ) Tj 2.372222 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 48.251029 Tz (Substrate ) Tj 2.819444 0 Td 56.944444 Tz (recogni ) Tj 51.428571 0 0 51.428571 0 1998.359223 Tm 6.338889 0 Td 47.800926 Tz (tion ) Tj 1.302778 0 Td 54.012346 Tz (has ) Tj 1.127778 0 Td 56.712963 Tz (been ) Tj 1.555556 0 Td 52.932099 Tz (suggested ) Tj 3.033333 0 Td 57.523148 Tz (from ) Tj 1.575 0 Td 47.222222 Tz (studies ) Tj 2.138889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 75.617284 Tz (NPP ) Tj 1.516667 0 Td 51.851852 Tz (family ) Tj 2.061111 0 Td 66.435185 Tz (domain ) Tj 51.428571 0 0 51.428571 0 1957.688645 Tm 6.377778 0 Td 57.928241 Tz (Swapping ) Tj 2.994444 0 Td 51.131687 Tz (chimeras. ) Tj 3.033333 0 Td 46.990741 Tz (In ) Tj 0.777778 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 48.611111 Tz (event, ) Tj 1.963889 0 Td 50.555556 Tz (these ) Tj 1.691667 0 Td 51.203704 Tz (previously ) Tj 3.325 0 Td 50.636574 Tz (reported ) Tj 51.428571 0 0 51.428571 0 1914.150617 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.018519 Tz (inhibitors ) Tj 2.975 0 Td 49.691358 Tz (are ) Tj 1.088889 0 Td 52.777778 Tz (analogs ) Tj 2.430556 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 60.763889 Tz (LPA, ) Tj 1.672222 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 51.103989 Tz (phospholipid, ) Tj 4.161111 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 50.771605 Tz (are ) Tj 51.428571 0 0 51.428571 0 1874.42654 Tm 6.358333 0 Td 61.574074 Tz (more ) Tj 1.613889 0 Td 55.387205 Tz (hydrophobic ) Tj 3.811111 0 Td 51.041667 Tz (than ) Tj 1.380556 0 Td 37.268519 Tz (is ) Tj 0.583333 0 Td 46.759259 Tz (typical ) Tj 2.080556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 47.530864 Tz (orally ) Tj 1.827778 0 Td 48.881173 Tz (bioavailable ) Tj 3.655556 0 Td 48.611111 Tz (drugs, ) Tj 51.428571 0 0 51.428571 0 1833.631879 Tm 6.338889 0 Td 52.314815 Tz (thereby ) Tj 2.411111 0 Td 48.206019 Tz (creating ) Tj 2.488889 0 Td 56.30787 Tz (problems ) Tj 2.897222 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 46.180556 Tz (that ) Tj 1.283333 0 Td 45.37037 Tz (area. ) Tj 51.428571 0 0 51.428571 0 1788.451815 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 0.952778 0 Td 48.611111 Tz (such, ) Tj 1.633333 0 Td 48.611111 Tz (there ) Tj 1.575 0 Td 45.37037 Tz (exists ) Tj 1.769444 0 Td 55.092593 Tz (a ) Tj 0.466667 0 Td 45.37037 Tz (definitive ) Tj 2.838889 0 Td 51.041667 Tz (lack ) Tj 1.341667 0 Td 46.990741 Tz (in ) Tj 0.7 0 Td 52.211934 Tz (providing ) Tj 2.936111 0 Td 46.8107 Tz (effective ) Tj 51.428571 0 0 51.428571 0 1745 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 46.666667 Tz (inhibition ) Tj 3.111111 0 Td 47.530864 Tz (\(or ) Tj 1.108333 0 Td 46.616809 Tz (inactivation\) ) Tj 3.927778 0 Td 50.231481 Tz (within ) Tj 2.1 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 49.537037 Tz (current ) Tj 2.333333 0 Td 68.055556 Tz (knowl ) Tj 51.428571 0 0 51.428571 0 1707.058537 Tm 6.358333 0 Td 57.523148 Tz (edge ) Tj 1.516667 0 Td 55.092593 Tz (base ) Tj 1.497222 0 Td 43.75 Tz (in ) Tj 0.719444 0 Td 42.939815 Tz (this ) Tj 1.186111 0 Td 47.314815 Tz (area, ) Tj 1.555556 0 Td 46.720679 Tz (particularly ) Tj 3.538889 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 32.407407 Tz (it ) Tj 0.563889 0 Td 53.472222 Tz (concerns ) Tj 2.741667 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 1662.621266 Tm 6.338889 0 Td 46.990741 Tz (that ) Tj 1.244444 0 Td 51.851852 Tz (not ) Tj 1.05 0 Td 52.662037 Tz (only ) Tj 1.380556 0 Td 48.148148 Tz (exhibit ) Tj 2.1 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 45.37037 Tz (inhibition, ) Tj 3.091667 0 Td 50.771605 Tz (but ) Tj 1.05 0 Td 46.990741 Tz (also ) Tj 1.302778 0 Td 58.333333 Tz (meet ) Tj 1.516667 0 Td 47.222222 Tz (certain ) Tj 2.1 0 Td 46.180556 Tz (oral ) Tj 52.857143 0 0 52.857143 0 1625.105534 Tm 6.167568 0 Td 45.195195 Tz (bioavailability ) Tj 4.540541 0 Td 50.713213 Tz (requirements ) Tj 4.105405 0 Td 44.144144 Tz (\(as ) Tj 1.267568 0 Td 55.968468 Tz (measured ) Tj 3.102703 0 Td 56.756757 Tz (by ) Tj 1.172973 0 Td 46.981982 Tz (Lipinskis ) Tj 51.428571 0 0 51.428571 0 1580.481074 Tm 6.358333 0 Td 43.055556 Tz (rules\). ) Tj 1.983333 0 Td 66.435185 Tz (As ) Tj 1.011111 0 Td 53.796296 Tz (noted ) Tj 1.788889 0 Td 51.851852 Tz (above, ) Tj 2.080556 0 Td 51.851852 Tz (previous ) Tj 2.683333 0 Td 51.041667 Tz (attempts ) Tj 2.644444 0 Td 45.37037 Tz (at ) Tj 0.738889 0 Td 54.282407 Tz (Such ) Tj 1.477778 0 Td 50.87963 Tz (treatments ) Tj 51.428571 0 0 51.428571 0 1540.788732 Tm 6.338889 0 Td 57.523148 Tz (have ) Tj 1.497222 0 Td 53.472222 Tz (provided ) Tj 2.741667 0 Td 55.362654 Tz (developments ) Tj 4.122222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 47.222222 Tz (certain ) Tj 2.138889 0 Td 47.685185 Tz (classes ) Tj 2.177778 0 Td 51.851852 Tz (of ) Tj 0.7 0 Td 62.294239 Tz (compounds ) Tj 40 0 0 40 0 1502 Tm 8.15 0 Td 60.416667 Tz (that ) Tj 1.6 0 Td 61.904762 Tz (exhibit ) Tj 2.75 0 Td 60.119048 Tz (certain ) Tj 2.725 0 Td 64.285714 Tz (desired ) Tj 2.875 0 Td 57.738095 Tz (results ) Tj 2.6 0 Td 68.75 Tz (with ) Tj 1.8 0 Td 69.345238 Tz (ATXinhibition. ) Tj 6.1 0 Td 112.5 Tz (How ) Tj 51.428571 0 0 51.428571 0 1457.619112 Tm 6.358333 0 Td 46.018519 Tz (ever, ) Tj 1.827778 0 Td 49.691358 Tz (the ) Tj 1.322222 0 Td 51.203704 Tz (generation ) Tj 3.538889 0 Td 58.333333 Tz (of ) Tj 1.030556 0 Td 48.611111 Tz (classes ) Tj 2.488889 0 Td 45.37037 Tz (that ) Tj 1.536111 0 Td 46.254209 Tz (effectively ) Tj 3.519444 0 Td 52.777778 Tz (provide ) Tj 40 0 0 40 0 1419 Tm 8.175 0 Td 65.740741 Tz (increased ) Tj 4 0 Td 60.119048 Tz (overall ) Tj 2.95 0 Td 98.611111 Tz (ATX ) Tj 2.25 0 Td 59.583333 Tz (inhibition ) Tj 4.025 0 Td 59.444444 Tz (characteristics ) Tj 5.775 0 Td 69.444444 Tz (has ) Tj 1.7 0 Td 75 Tz (been ) Tj 51.428571 0 0 51.428571 0 1376.892989 Tm 6.358333 0 Td 51.388889 Tz (lacking ) Tj 2.333333 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 53.009259 Tz (pharmaceutical ) Tj 4.666667 0 Td 45.730453 Tz (industry. ) Tj 38.571429 0 0 38.571429 0 1299 Tm 10.292593 0 Td 105.432099 Tz (ADVANTAGES ) Tj 6.559259 0 Td 115.226337 Tz (AND ) Tj 2.359259 0 Td 89.012346 Tz (BRIEF ) Tj 3.007407 0 Td 94.276094 Tz (DESCRIPTION ) Tj 6.507407 0 Td 99.382716 Tz (OF ) Tj 38.571429 0 0 38.571429 0 1257 Tm 16.385185 0 Td 105.144033 Tz (THE ) Tj 2.177778 0 Td 98.422497 Tz (INVENTION ) Tj 51.428571 0 0 51.428571 0 1169.921773 Tm 7.116667 0 Td 35.648148 Tz (It ) Tj 0.622222 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 50.231481 Tz (thus ) Tj 1.419444 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 54.73251 Tz (advantage ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 50.462963 Tz (present ) Tj 2.333333 0 Td 49.331276 Tz (invention ) Tj 2.877778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 53.240741 Tz (provide ) Tj 51.428571 0 0 51.428571 0 1126.377358 Tm 6.358333 0 Td 45.775463 Tz (reliable ) Tj 2.313889 0 Td 50.05144 Tz (autotaxin ) Tj 2.858333 0 Td 46.720679 Tz (inactivators ) Tj 3.519444 0 Td 47.530864 Tz (for ) Tj 0.952778 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 55.555556 Tz (purpose ) Tj 2.488889 0 Td 55.092593 Tz (of ) Tj 0.719444 0 Td 53.472222 Tz (reducing ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1085.115942 Tm 6.358333 0 Td 52.5 Tz (conversion ) Tj 3.286111 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 73.45679 Tz (LPC ) Tj 1.458333 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 71.296296 Tz (LPA ) Tj 1.438889 0 Td 53.240741 Tz (through ) Tj 2.391667 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 44.191919 Tz (utilization ) Tj 3.052778 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 48.148148 Tz (readily ) Tj 51.428571 0 0 51.428571 0 1046.296167 Tm 6.358333 0 Td 48.251029 Tz (available ) Tj 2.702778 0 Td 59.41358 Tz (and ) Tj 1.147222 0 Td 47.530864 Tz (easily ) Tj 1.827778 0 Td 56.712963 Tz (produced ) Tj 2.858333 0 Td 63.599537 Tz (compound ) Tj 3.169444 0 Td 48.611111 Tz (\(or ) Tj 0.972222 0 Td 59.953704 Tz (compounds\) ) Tj 3.694444 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 1002.936842 Tm 6.358333 0 Td 55.092593 Tz (does ) Tj 1.672222 0 Td 49.691358 Tz (not ) Tj 1.166667 0 Td 56.712963 Tz (pose ) Tj 1.652778 0 Td 57.253086 Tz (any ) Tj 1.361111 0 Td 45.959596 Tz (significant ) Tj 3.286111 0 Td 49.691358 Tz (health ) Tj 2.1 0 Td 45.37037 Tz (risks ) Tj 1.672222 0 Td 59.41358 Tz (and ) Tj 1.361111 0 Td 48.148148 Tz (exhibit ) Tj 2.313889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 963.333333 Tm 6.358333 0 Td 52.211934 Tz (necessary ) Tj 3.033333 0 Td 46.990741 Tz (oral ) Tj 1.322222 0 Td 46.450617 Tz (bioavailability ) Tj 4.413889 0 Td 50.854701 Tz (requirements. ) Tj 4.161111 0 Td 56.944444 Tz (Another ) Tj 2.566667 0 Td 65.462963 Tz (advan ) Tj 51.428571 0 0 51.428571 0 920.46875 Tm 6.338889 0 Td 51.851852 Tz (tage ) Tj 1.516667 0 Td 40.509259 Tz (is ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 44.444444 Tz (ability ) Tj 2.158333 0 Td 48.611111 Tz (for ) Tj 1.127778 0 Td 51.131687 Tz (treatment ) Tj 3.052778 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 55.092593 Tz (such ) Tj 1.594444 0 Td 62.294239 Tz (compounds ) Tj 3.694444 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 879.683841 Tm 6.358333 0 Td 53.472222 Tz (cancer ) Tj 2.022222 0 Td 51.527778 Tz (prevention ) Tj 3.266667 0 Td 51.131687 Tz (treatment ) Tj 2.916667 0 Td 51.49177 Tz (regimens. ) Tj 2.955556 0 Td 50.771605 Tz (yet ) Tj 1.05 0 Td 52.314815 Tz (another ) Tj 2.333333 0 Td 54.372428 Tz (advantage ) Tj 51.428571 0 0 51.428571 0 837.141291 Tm 6.358333 0 Td 38.888889 Tz (is ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 47.170782 Tz (potential ) Tj 2.741667 0 Td 47.962963 Tz (capability ) Tj 3.091667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 52.572016 Tz (providing ) Tj 3.033333 0 Td 54.282407 Tz (combinations ) Tj 4.122222 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 58.333333 Tz (dif ) Tj 51.428571 0 0 51.428571 0 793.672372 Tm 6.358333 0 Td 48.070988 Tz (ferent ) Tj 1.944444 0 Td 61.574074 Tz (compounds ) Tj 3.558333 0 Td 46.180556 Tz (that ) Tj 1.341667 0 Td 49.691358 Tz (are ) Tj 1.127778 0 Td 48.611111 Tz (similar ) Tj 2.236111 0 Td 46.990741 Tz (in ) Tj 0.797222 0 Td 51.041667 Tz (foundational ) Tj 3.908333 0 Td 47.530864 Tz (structure ) Tj 51.428571 0 0 51.428571 0 753.460993 Tm 6.338889 0 Td 46.990741 Tz (that ) Tj 1.244444 0 Td 66.975309 Tz (may ) Tj 1.361111 0 Td 47.685185 Tz (exhibit ) Tj 2.1 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 47.43266 Tz (synergistic ) Tj 3.266667 0 Td 45.37037 Tz (effect ) Tj 1.769444 0 Td 47.530864 Tz (for ) Tj 0.972222 0 Td 47.222222 Tz (further ) Tj 2.061111 0 Td 57.928241 Tz (improved ) Tj 2.858333 0 Td 77.777778 Tz (ATX ) Tj 40 0 0 40 0 717 Tm 8.175 0 Td 58.333333 Tz (inhibition. ) Tj 51.428571 0 0 51.428571 0 671.12766 Tm 7.097222 0 Td 52.121914 Tz (Accordingly, ) Tj 4.083333 0 Td 44.560185 Tz (this ) Tj 1.438889 0 Td 49.331276 Tz (invention ) Tj 3.013889 0 Td 57.449495 Tz (encompasses ) Tj 4.161111 0 Td 55.092593 Tz (a ) Tj 0.7 0 Td 59.41358 Tz (method ) Tj 2.488889 0 Td 48.611111 Tz (for ) Tj 51.428571 0 0 51.428571 0 629.22549 Tm 6.338889 0 Td 46.990741 Tz (treating ) Tj 2.411111 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 47.222222 Tz (patient ) Tj 2.158333 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 52.932099 Tz (reduce ) Tj 2.080556 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 44.965278 Tz (activity ) Tj 2.372222 0 Td 50.771605 Tz (within ) Tj 1.983333 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 69.135802 Tz (Sub ) Tj 51.428571 0 0 51.428571 0 588.034525 Tm 6.319444 0 Td 46.180556 Tz (ject ) Tj 1.341667 0 Td 46.090535 Tz (patients ) Tj 2.741667 0 Td 53.148148 Tz (body, ) Tj 1.866667 0 Td 48.611111 Tz (said ) Tj 1.458333 0 Td 59.953704 Tz (method ) Tj 2.391667 0 Td 51.131687 Tz (involving ) Tj 2.994444 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 49.691358 Tz (introduction ) Tj 51.428571 0 0 51.428571 0 545.580488 Tm 6.338889 0 Td 51.851852 Tz (within ) Tj 2.061111 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 49.074074 Tz (Subject ) Tj 2.216667 0 Td 48.148148 Tz (patient ) Tj 2.197222 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 46.990741 Tz (at ) Tj 0.738889 0 Td 44.722222 Tz (least ) Tj 1.536111 0 Td 59.41358 Tz (one ) Tj 1.263889 0 Td 63.599537 Tz (compound ) Tj 3.247222 0 Td 49.421296 Tz (selected ) Tj 51.428571 0 0 51.428571 0 505 Tm 6.358333 0 Td 58.333333 Tz (from ) Tj 1.516667 0 Td 51.851852 Tz (the ) Tj 1.030556 0 Td 56.388889 Tz (group ) Tj 1.847222 0 Td 49.583333 Tz (consisting ) Tj 3.091667 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 43.75 Tz (at ) Tj 0.641667 0 Td 45.37037 Tz (least ) Tj 1.497222 0 Td 57.253086 Tz (one ) Tj 1.166667 0 Td 53.324916 Tz (naphthalene ) Tj 3.636111 0 Td 47.800926 Tz (Sulfone, ) Tj 51.428571 0 0 51.428571 0 463.899225 Tm 6.358333 0 Td 45.37037 Tz (at ) Tj 0.855556 0 Td 44.074074 Tz (least ) Tj 1.633333 0 Td 58.333333 Tz (one ) Tj 1.322222 0 Td 51.388889 Tz (phenylsulfone, ) Tj 4.627778 0 Td 43.75 Tz (at ) Tj 0.855556 0 Td 44.074074 Tz (least ) Tj 1.613889 0 Td 59.41358 Tz (one ) Tj 1.341667 0 Td 51.388889 Tz (peptide ) Tj 2.488889 0 Td 50.771605 Tz (including ) Tj 51.428571 0 0 51.428571 0 418.64 Tm 6.338889 0 Td 50.771605 Tz (unnatural ) Tj 2.955556 0 Td 60.277778 Tz (amino ) Tj 1.983333 0 Td 46.990741 Tz (acids, ) Tj 1.847222 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 52.256944 Tz (mixtures ) Tj 2.683333 0 Td 46.585648 Tz (thereof. ) Tj 51.428571 0 0 51.428571 0 376.549313 Tm 7.097222 0 Td 52.662037 Tz (This ) Tj 1.438889 0 Td 48.611111 Tz (inventive ) Tj 2.8 0 Td 59.41358 Tz (method ) Tj 2.255556 0 Td 51.041667 Tz (thus ) Tj 1.361111 0 Td 53.472222 Tz (concerns ) Tj 2.722222 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 48.611111 Tz (treatment, ) Tj 3.072222 0 Td 48.611111 Tz (via ) Tj 0.991667 0 Td 59.41358 Tz (any ) Tj 51.428571 0 0 51.428571 0 336.38756 Tm 6.358333 0 Td 48.251029 Tz (available ) Tj 2.761111 0 Td 54.62963 Tz (manner, ) Tj 2.45 0 Td 55.092593 Tz (such ) Tj 1.477778 0 Td 48.611111 Tz (as ) Tj 0.758333 0 Td 49.151235 Tz (intravenous, ) Tj 3.694444 0 Td 46.180556 Tz (oral ) Tj 1.283333 0 Td 46.990741 Tz (ingestion, ) Tj 2.936111 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 295.624849 Tm 6.358333 0 Td 42.12963 Tz (like, ) Tj 1.438889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 62.654321 Tz (mammalian ) Tj 3.597222 0 Td 48.611111 Tz (Subject ) Tj 2.197222 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 53.472222 Tz (reduce ) Tj 2.080556 0 Td 49.691358 Tz (autotaxin ) Tj 2.877778 0 Td 45.100309 Tz (availability ) Tj 51.428571 0 0 51.428571 0 253.25 Tm 6.338889 0 Td 45.775463 Tz (therein. ) Tj 2.469444 0 Td 59.143519 Tz (Such ) Tj 1.633333 0 Td 58.333333 Tz (an ) Tj 0.952778 0 Td 48.611111 Tz (inventive ) Tj 2.877778 0 Td 59.953704 Tz (method ) Tj 2.411111 0 Td 66.975309 Tz (may ) Tj 1.419444 0 Td 49.421296 Tz (also ) Tj 1.419444 0 Td 58.693416 Tz (encompass ) Tj 3.422222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 211.02515 Tm 6.338889 0 Td 56.388889 Tz (broad ) Tj 1.827778 0 Td 51.131687 Tz (treatment ) Tj 2.877778 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 61.574074 Tz (same ) Tj 1.613889 0 Td 49.537037 Tz (subject ) Tj 2.216667 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 61.574074 Tz (number ) Tj 2.313889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.450617 Tz (different ) Tj 51.428571 0 0 51.428571 0 170.470886 Tm 6.358333 0 Td 53.877315 Tz (maladies ) Tj 2.936111 0 Td 49.907407 Tz (associated ) Tj 3.363889 0 Td 52.662037 Tz (with ) Tj 1.633333 0 Td 50.05144 Tz (autotaxin ) Tj 3.052778 0 Td 53.472222 Tz (presence ) Tj 2.897222 0 Td 59.41358 Tz (and ) Tj 1.419444 0 Td 45.37037 Tz (activity ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 33.775 0 Td 77.777778 Tz (4 ) Tj 51.428571 0 0 51.428571 0 2916.086538 Tm 25.277778 0 Td 51.851852 Tz (within ) Tj 2.002778 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 53.472222 Tz (subjects ) Tj 2.702778 0 Td 59.953704 Tz (body ) Tj 1.613889 0 Td 51.203704 Tz (\(such ) Tj 1.691667 0 Td 48.611111 Tz (as ) Tj 0.738889 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 43.425926 Tz (treat ) Tj 1.4 0 Td 46.585648 Tz (obesity, ) Tj 2.372222 0 Td 53.148148 Tz (atheroscle ) Tj 51.428571 0 0 51.428571 0 2873.046632 Tm 25.297222 0 Td 43.209877 Tz (rosis, ) Tj 1.788889 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 50.771605 Tz (the ) Tj 1.186111 0 Td 40.833333 Tz (like, ) Tj 1.458333 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 53.148148 Tz (noted ) Tj 1.827778 0 Td 46.585648 Tz (herein\), ) Tj 2.488889 0 Td 48.070988 Tz (rather ) Tj 1.944444 0 Td 51.851852 Tz (than ) Tj 1.497222 0 Td 54.552469 Tz (simply ) Tj 2.255556 0 Td 47.530864 Tz (for ) Tj 40 0 0 40 0 2838 Tm 32.525 0 Td 68.75 Tz (cancer ) Tj 2.65 0 Td 65 Tz (treatments ) Tj 4.15 0 Td 61.805556 Tz (alone. ) Tj 51.428571 0 0 51.428571 0 2789.845333 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.438889 0 Td 48.611111 Tz (inventive ) Tj 2.897222 0 Td 62.294239 Tz (compounds ) Tj 3.636111 0 Td 47.530864 Tz (for ) Tj 1.127778 0 Td 54.282407 Tz (such ) Tj 1.594444 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 59.953704 Tz (method ) Tj 2.411111 0 Td 57.523148 Tz (have ) Tj 1.613889 0 Td 59.143519 Tz (been ) Tj 51.428571 0 0 51.428571 0 2750.651075 Tm 25.297222 0 Td 55.092593 Tz (developed ) Tj 3.227778 0 Td 45.37037 Tz (in ) Tj 0.816667 0 Td 45.775463 Tz (relation ) Tj 2.488889 0 Td 42.12963 Tz (to ) Tj 0.816667 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 47.314815 Tz (inhibition ) Tj 3.072222 0 Td 47.638889 Tz (capability ) Tj 3.111111 0 Td 65.895062 Tz (pre ) Tj 51.428571 0 0 51.428571 0 2710.746479 Tm 25.297222 0 Td 49.691358 Tz (dicted ) Tj 1.925 0 Td 53.703704 Tz (through ) Tj 2.411111 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 53.06713 Tz (modified ) Tj 2.663889 0 Td 58.582621 Tz (pharmacophore ) Tj 4.725 0 Td 56.712963 Tz (modeling ) Tj 2.858333 0 Td 49.016204 Tz (process. ) Tj 51.428571 0 0 51.428571 0 2666.772182 Tm 25.316667 0 Td 46.990741 Tz (In ) Tj 0.719444 0 Td 50.231481 Tz (essence, ) Tj 2.547222 0 Td 50.555556 Tz (these ) Tj 1.672222 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 50.925926 Tz (derived ) Tj 2.255556 0 Td 54.166667 Tz (through ) Tj 2.430556 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 39.814815 Tz (initial ) Tj 51.428571 0 0 51.428571 0 2625.387214 Tm 25.277778 0 Td 44.781145 Tz (utilization ) Tj 3.188889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 64.814815 Tz (known ) Tj 2.177778 0 Td 46.666667 Tz (structures ) Tj 2.994444 0 Td 48.611111 Tz (to ) Tj 0.797222 0 Td 54.166667 Tz (develop ) Tj 2.469444 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 58.333333 Tz (pharmacophore ) Tj 51.428571 0 0 51.428571 0 2584.371901 Tm 25.297222 0 Td 58.333333 Tz (from ) Tj 1.536111 0 Td 59.62963 Tz (which ) Tj 1.905556 0 Td 47.685185 Tz (further ) Tj 2.1 0 Td 55.387205 Tz (comparisons ) Tj 3.811111 0 Td 68.055556 Tz (may ) Tj 1.322222 0 Td 59.953704 Tz (be ) Tj 0.855556 0 Td 57.037037 Tz (made. ) Tj 1.847222 0 Td 63.518519 Tz (Sucha ) Tj 2.022222 0 Td 57.253086 Tz (ligand ) Tj 51.428571 0 0 51.428571 0 2542.046229 Tm 25.277778 0 Td 55.740741 Tz (based ) Tj 1.886111 0 Td 58.582621 Tz (pharmacophore ) Tj 4.783333 0 Td 50.231481 Tz (includes ) Tj 2.644444 0 Td 46.450617 Tz (six ) Tj 1.05 0 Td 44.560185 Tz (distinct ) Tj 2.352778 0 Td 54.282407 Tz (base ) Tj 1.516667 0 Td 50.555556 Tz (point ) Tj 1.711111 0 Td 64.00463 Tz (func ) Tj 51.428571 0 0 51.428571 0 2500.643564 Tm 25.277778 0 Td 47.314815 Tz (tions ) Tj 1.652778 0 Td 44.560185 Tz (that ) Tj 1.263889 0 Td 54.552469 Tz (appear ) Tj 2.119444 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 58.333333 Tz (be ) Tj 0.875 0 Td 50.925926 Tz (present ) Tj 2.294444 0 Td 51.311728 Tz (within ) Tj 2.061111 0 Td 55.092593 Tz (each ) Tj 1.516667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 50.87963 Tz (previously ) Tj 51.428571 0 0 51.428571 0 2456.815944 Tm 25.297222 0 Td 64.814815 Tz (known ) Tj 2.1 0 Td 45.075758 Tz (structures, ) Tj 3.091667 0 Td 54.62963 Tz (interms ) Tj 2.430556 0 Td 51.851852 Tz (of ) Tj 0.7 0 Td 56.388889 Tz (group ) Tj 1.808333 0 Td 47.800926 Tz (size ) Tj 1.244444 0 Td 59.41358 Tz (and ) Tj 1.166667 0 Td 49.826389 Tz (distance ) Tj 2.488889 0 Td 58.333333 Tz (between ) Tj 51.428571 0 0 51.428571 0 2414.997506 Tm 25.297222 0 Td 47.962963 Tz (functions, ) Tj 3.091667 0 Td 44.560185 Tz (that ) Tj 1.263889 0 Td 59.62963 Tz (would ) Tj 2.002778 0 Td 46.666667 Tz (react ) Tj 1.575 0 Td 46.990741 Tz (in ) Tj 0.719444 0 Td 48.611111 Tz (a ) Tj 0.486111 0 Td 54.012346 Tz (proper ) Tj 2.119444 0 Td 50 Tz (fashion ) Tj 2.294444 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2373.728155 Tm 25.297222 0 Td 55.902778 Tz (molecule ) Tj 2.819444 0 Td 50.771605 Tz (\(of ) Tj 0.991667 0 Td 48.611111 Tz (large ) Tj 1.594444 0 Td 43.425926 Tz (size, ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.797222 0 Td 52.5 Tz (noted ) Tj 1.691667 0 Td 55.092593 Tz (above\) ) Tj 2.119444 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 48.611111 Tz (deactivate ) Tj 3.091667 0 Td 53.472222 Tz (Such ) Tj 1.438889 0 Td 61.574074 Tz (an ) Tj 51.428571 0 0 51.428571 0 2336.620818 Tm 25.297222 0 Td 63.194444 Tz (enzyme ) Tj 2.469444 0 Td 58.333333 Tz (from ) Tj 1.613889 0 Td 51.527778 Tz (converting ) Tj 3.325 0 Td 72.376543 Tz (LPC ) Tj 1.536111 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 59.143519 Tz (LPA. ) Tj 1.672222 0 Td 49.907407 Tz (Generally, ) Tj 3.208333 0 Td 49.259259 Tz (eight ) Tj 1.652778 0 Td 65.895062 Tz (pre ) Tj 51.428571 0 0 51.428571 0 2293.16707 Tm 25.297222 0 Td 50.925926 Tz (viously ) Tj 2.372222 0 Td 45.37037 Tz (identified ) Tj 2.955556 0 Td 48.971193 Tz (non-lipid ) Tj 2.8 0 Td 78.858025 Tz (ATX ) Tj 1.613889 0 Td 46.342593 Tz (inhibitors ) Tj 2.994444 0 Td 59.953704 Tz (were ) Tj 1.613889 0 Td 44.722222 Tz (built ) Tj 1.536111 0 Td 52.5 Tz (using ) Tj 51.428571 0 0 51.428571 0 2251.379571 Tm 25.297222 0 Td 89.660494 Tz (MOE ) Tj 1.827778 0 Td 60.493827 Tz (and ) Tj 1.322222 0 Td 50.925926 Tz (ionized ) Tj 2.352778 0 Td 51.851852 Tz (as ) Tj 0.875 0 Td 50.05144 Tz (predicted ) Tj 2.916667 0 Td 46.990741 Tz (at ) Tj 0.777778 0 Td 48.611111 Tz (biological ) Tj 3.15 0 Td 74.537037 Tz (pH ) Tj 1.127778 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 55.092593 Tz (emulate ) Tj 51.428571 0 0 51.428571 0 2209.434007 Tm 25.297222 0 Td 46.180556 Tz (internal ) Tj 2.45 0 Td 50.925926 Tz (metabolization ) Tj 4.491667 0 Td 43.518519 Tz (possibilities. ) Tj 3.908333 0 Td 59.143519 Tz (Such ) Tj 1.613889 0 Td 62.294239 Tz (compounds ) Tj 3.597222 0 Td 59.143519 Tz (were ) Tj 51.428571 0 0 51.428571 0 2168.368944 Tm 25.277778 0 Td 52.662037 Tz (then ) Tj 1.497222 0 Td 45.37037 Tz (flexibly ) Tj 2.391667 0 Td 51.388889 Tz (aligned ) Tj 2.352778 0 Td 54.282407 Tz (onto ) Tj 1.497222 0 Td 59.41358 Tz (one ) Tj 1.263889 0 Td 52.777778 Tz (another ) Tj 2.411111 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 46.990741 Tz (identify ) Tj 2.469444 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 57.685185 Tz (afore ) Tj 51.428571 0 0 51.428571 0 2123.995074 Tm 25.297222 0 Td 56.893004 Tz (mentioned ) Tj 3.344444 0 Td 48.935185 Tz (functional ) Tj 3.227778 0 Td 54.552469 Tz (groups ) Tj 2.236111 0 Td 46.990741 Tz (that ) Tj 1.380556 0 Td 51.851852 Tz (share ) Tj 1.827778 0 Td 70.216049 Tz (common ) Tj 2.819444 0 Td 54.282407 Tz (Volumes. ) Tj 51.428571 0 0 51.428571 0 2085.245943 Tm 25.297222 0 Td 63.734568 Tz (The ) Tj 1.361111 0 Td 47.530864 Tz (six ) Tj 1.088889 0 Td 46.018519 Tz (identified ) Tj 2.994444 0 Td 58.084046 Tz (pharmacophore ) Tj 4.744444 0 Td 53.472222 Tz (base ) Tj 1.516667 0 Td 49.691358 Tz (points ) Tj 2.041667 0 Td 52.5 Tz (were, ) Tj 1.827778 0 Td 48.611111 Tz (as ) Tj 0.836111 0 Td 58.333333 Tz (fol ) Tj 51.428571 0 0 51.428571 0 2044.113721 Tm 25.297222 0 Td 51.203704 Tz (lows: ) Tj 1.730556 0 Td 56.712963 Tz (an ) Tj 0.875 0 Td 50.925926 Tz (anionic ) Tj 2.313889 0 Td 57.037037 Tz (group ) Tj 1.925 0 Td 48.070988 Tz (\(point ) Tj 1.963889 0 Td 39.969136 Tz (1\), ) Tj 0.894444 0 Td 60.493827 Tz (two ) Tj 1.263889 0 Td 57.523148 Tz (hydrogen ) Tj 2.936111 0 Td 61.574074 Tz (bond ) Tj 1.672222 0 Td 62.87037 Tz (accep ) Tj 51.428571 0 0 51.428571 0 2002.313237 Tm 25.277778 0 Td 48.611111 Tz (tors/metal ) Tj 3.266667 0 Td 44.560185 Tz (ligators ) Tj 2.469444 0 Td 47.685185 Tz (\(points ) Tj 2.352778 0 Td 58.333333 Tz (2 ) Tj 0.680556 0 Td 58.333333 Tz (and ) Tj 1.361111 0 Td 42.12963 Tz (4\), ) Tj 1.088889 0 Td 60.493827 Tz (two ) Tj 1.419444 0 Td 52.662037 Tz (aromatic ) Tj 2.838889 0 Td 55.632716 Tz (groups ) Tj 51.428571 0 0 51.428571 0 1960.364676 Tm 25.316667 0 Td 46.759259 Tz (\(points ) Tj 2.197222 0 Td 55.092593 Tz (3 ) Tj 0.544444 0 Td 60.493827 Tz (and ) Tj 1.263889 0 Td 42.12963 Tz (5\), ) Tj 0.952778 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 59.41358 Tz (one ) Tj 1.244444 0 Td 57.118056 Tz (hydrogen ) Tj 2.916667 0 Td 62.384259 Tz (bond ) Tj 1.672222 0 Td 57.685185 Tz (donor ) Tj 1.905556 0 Td 48.070988 Tz (\(point ) Tj 1.944444 0 Td 41.049383 Tz (6\). ) Tj 0.991667 0 Td 48.611111 Tz (In ) Tj 51.428571 0 0 51.428571 0 1918.47914 Tm 25.277778 0 Td 54.444444 Tz (terms ) Tj 1.944444 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 40.277778 Tz (initial ) Tj 2.022222 0 Td 55.092593 Tz (comparisons ) Tj 3.947222 0 Td 53.472222 Tz (with ) Tj 1.575 0 Td 65.462963 Tz (known ) Tj 2.294444 0 Td 63.599537 Tz (compound ) Tj 3.363889 0 Td 59.953704 Tz (data ) Tj 51.428571 0 0 51.428571 0 1877.675676 Tm 25.277778 0 Td 49.151235 Tz (bases, ) Tj 1.963889 0 Td 43.75 Tz (this ) Tj 1.283333 0 Td 47.890947 Tz (six-point ) Tj 2.761111 0 Td 55.497685 Tz (approach ) Tj 2.858333 0 Td 56.17284 Tz (proved ) Tj 2.216667 0 Td 50.771605 Tz (too ) Tj 1.127778 0 Td 42.669753 Tz (restrictive; ) Tj 3.325 0 Td 56.712963 Tz (no ) Tj 0.875 0 Td 44.560185 Tz (hits ) Tj 51.428571 0 0 51.428571 0 1833.081633 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.652778 0 Td 57.037037 Tz (found ) Tj 1.925 0 Td 48.611111 Tz (for ) Tj 1.088889 0 Td 47.685185 Tz (further ) Tj 2.216667 0 Td 42.939815 Tz (testing. ) Tj 2.313889 0 Td 54.444444 Tz (Thus, ) Tj 1.847222 0 Td 35.648148 Tz (it ) Tj 0.641667 0 Td 61.574074 Tz (was ) Tj 1.380556 0 Td 53.472222 Tz (reasoned ) Tj 2.8 0 Td 45.37037 Tz (that ) Tj 1.302778 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1797.061758 Tm 25.297222 0 Td 57.361111 Tz (pared-down ) Tj 3.577778 0 Td 55.902778 Tz (approach ) Tj 2.838889 0 Td 62.654321 Tz (was ) Tj 1.302778 0 Td 51.851852 Tz (necessary ) Tj 2.936111 0 Td 48.611111 Tz (to ) Tj 0.738889 0 Td 51.446759 Tz (generate ) Tj 2.625 0 Td 56.17284 Tz (any ) Tj 1.205556 0 Td 46.990741 Tz (Suitable ) Tj 48.571429 0 0 48.571429 0 1751 Tm 26.764706 0 Td 46.323529 Tz (hits ) Tj 1.297059 0 Td 46.323529 Tz (at ) Tj 0.679412 0 Td 40.318627 Tz (all. ) Tj 1.194118 0 Td 48.039216 Tz (In ) Tj 0.741176 0 Td 46.323529 Tz (this ) Tj 1.297059 0 Td 58.333333 Tz (manner, ) Tj 2.635294 0 Td 34.313725 Tz (it ) Tj 0.576471 0 Td 64.052288 Tz (was ) Tj 1.358824 0 Td 56.372549 Tz (decided ) Tj 2.532353 0 Td 48.039216 Tz (to ) Tj 0.761765 0 Td 63.480392 Tz (remove ) Tj 2.429412 0 Td 61.764706 Tz (one ) Tj 1.276471 0 Td 58.333333 Tz (of ) Tj 0.761765 0 Td 54.901961 Tz (the ) Tj 51.428571 0 0 51.428571 0 1710.353535 Tm 25.297222 0 Td 52.662037 Tz (aromatic ) Tj 2.761111 0 Td 49.691358 Tz (points ) Tj 2.022222 0 Td 51.851852 Tz (as ) Tj 0.855556 0 Td 51.851852 Tz (well ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 58.333333 Tz (one ) Tj 1.302778 0 Td 55.092593 Tz (of ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 57.118056 Tz (hydrogen ) Tj 2.994444 0 Td 54.444444 Tz (bond/metal ) Tj 51.428571 0 0 51.428571 0 1669.041237 Tm 25.297222 0 Td 45.833333 Tz (ligator ) Tj 2.080556 0 Td 49.691358 Tz (points ) Tj 2.002778 0 Td 48.148148 Tz (\(points ) Tj 2.255556 0 Td 43.75 Tz (2, ) Tj 0.719444 0 Td 46.990741 Tz (3, ) Tj 0.758333 0 Td 46.990741 Tz (4, ) Tj 0.777778 0 Td 51.851852 Tz (or ) Tj 0.816667 0 Td 43.209877 Tz (5\), ) Tj 0.972222 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 54.012346 Tz (reduce ) Tj 2.119444 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 61.033951 Tz (number ) Tj 2.411111 0 Td 56.712963 Tz (of ) Tj 52.857143 0 0 52.857143 0 1629.236613 Tm 24.613514 0 Td 47.822823 Tz (points ) Tj 2.118919 0 Td 50.1001 Tz (necessary ) Tj 3.064865 0 Td 50.45045 Tz (for ) Tj 1.210811 0 Td 50.844595 Tz (database ) Tj 2.781081 0 Td 52.027027 Tz (comparisons. ) Tj 4.124324 0 Td 47.054747 Tz (Additionally, ) Tj 51.428571 0 0 51.428571 0 1583.859155 Tm 25.277778 0 Td 54.282407 Tz (however, ) Tj 2.761111 0 Td 32.407407 Tz (it ) Tj 0.505556 0 Td 61.574074 Tz (was ) Tj 1.225 0 Td 53.472222 Tz (hypothesized ) Tj 3.966667 0 Td 45.37037 Tz (that ) Tj 1.244444 0 Td 54.62963 Tz (removal ) Tj 2.430556 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.85755 Tz (consideration ) Tj 4.025 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1542.6924 Tm 25.297222 0 Td 57.253086 Tz (any ) Tj 1.186111 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 49.907407 Tz (these ) Tj 1.613889 0 Td 49.691358 Tz (points ) Tj 1.944444 0 Td 61.574074 Tz (was ) Tj 1.263889 0 Td 47.395833 Tz (suitable ) Tj 2.411111 0 Td 58.333333 Tz (due ) Tj 1.186111 0 Td 45.37037 Tz (to ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 54.282407 Tz (expected ) Tj 2.761111 0 Td 49.331276 Tz (chelation ) Tj 51.428571 0 0 51.428571 0 1501.222778 Tm 25.297222 0 Td 59.143519 Tz (most ) Tj 1.633333 0 Td 45.37037 Tz (likely ) Tj 1.847222 0 Td 49.691358 Tz (prevalent ) Tj 2.897222 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 48.611111 Tz (divalent ) Tj 2.547222 0 Td 51.311728 Tz (metals ) Tj 2.1 0 Td 43.75 Tz (in ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 48.611111 Tz (active ) Tj 1.944444 0 Td 38.888889 Tz (site. ) Tj 51.428571 0 0 51.428571 0 1461.858182 Tm 25.297222 0 Td 63.734568 Tz (The ) Tj 1.4 0 Td 46.090535 Tz (resultant ) Tj 2.722222 0 Td 51.851852 Tz (four ) Tj 1.477778 0 Td 50 Tz (5-point ) Tj 2.333333 0 Td 56.944444 Tz (pharmacophores ) Tj 5.055556 0 Td 59.143519 Tz (were ) Tj 1.633333 0 Td 52.932099 Tz (generated ) Tj 51.428571 0 0 51.428571 0 1418.989744 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 55.902778 Tz (each ) Tj 1.555556 0 Td 51.388889 Tz (lacking ) Tj 2.372222 0 Td 58.333333 Tz (one ) Tj 1.263889 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (points ) Tj 2.041667 0 Td 43.75 Tz (2, ) Tj 0.738889 0 Td 45.37037 Tz (3, ) Tj 0.777778 0 Td 43.75 Tz (4, ) Tj 0.738889 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 45.37037 Tz (5; ) Tj 0.758333 0 Td 46.367521 Tz (additionally, ) Tj 51.428571 0 0 51.428571 0 1379.992656 Tm 25.297222 0 Td 51.851852 Tz (four ) Tj 1.477778 0 Td 50.462963 Tz (4-point ) Tj 2.352778 0 Td 57.407407 Tz (pharmacophores ) Tj 5.113889 0 Td 59.143519 Tz (were ) Tj 1.672222 0 Td 52.572016 Tz (generated ) Tj 3.091667 0 Td 55.092593 Tz (each ) Tj 1.633333 0 Td 50.462963 Tz (lacking ) Tj 51.428571 0 0 51.428571 0 1336.444444 Tm 25.297222 0 Td 58.333333 Tz (one ) Tj 1.205556 0 Td 53.06713 Tz (aromatic ) Tj 2.722222 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 59.41358 Tz (one ) Tj 1.244444 0 Td 56.712963 Tz (hydrogen ) Tj 2.897222 0 Td 61.574074 Tz (bond ) Tj 1.633333 0 Td 51.157407 Tz (acceptor/metal ) Tj 4.472222 0 Td 42.12963 Tz (ligator. ) Tj 51.428571 0 0 51.428571 0 1293.42454 Tm 25.316667 0 Td 64.00463 Tz (From ) Tj 1.75 0 Td 44.560185 Tz (this ) Tj 1.263889 0 Td 45.910494 Tz (basis, ) Tj 1.866667 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 47.395833 Tz (suitable ) Tj 2.527778 0 Td 61.574074 Tz (number ) Tj 2.391667 0 Td 58.333333 Tz (of ) Tj 0.836111 0 Td 51.851852 Tz (nine ) Tj 1.458333 0 Td 57.175926 Tz (pharmacophores ) Tj 51.428571 0 0 51.428571 0 1249 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.594444 0 Td 54.282407 Tz (each ) Tj 1.497222 0 Td 55.092593 Tz (used ) Tj 1.477778 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 50.231481 Tz (search ) Tj 2.002778 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 51.851852 Tz (National ) Tj 2.644444 0 Td 58.333333 Tz (Cancer ) Tj 2.236111 0 Td 43.930041 Tz (Institute ) Tj 2.547222 0 Td 57.037037 Tz (\(NCI\) ) Tj 51.428571 0 0 51.428571 0 1211.312732 Tm 25.316667 0 Td 55.092593 Tz (Database ) Tj 2.858333 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 58.333333 Tz (any ) Tj 1.263889 0 Td 62.294239 Tz (compounds ) Tj 3.577778 0 Td 50 Tz (present ) Tj 2.313889 0 Td 45.775463 Tz (therein. ) Tj 2.430556 0 Td 64.00463 Tz (From ) Tj 1.769444 0 Td 45.37037 Tz (there, ) Tj 1.866667 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1169.769784 Tm 25.297222 0 Td 37.268519 Tz (list ) Tj 1.011111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 60.493827 Tz (254 ) Tj 1.225 0 Td 61.934156 Tz (compounds ) Tj 3.461111 0 Td 62.654321 Tz (was ) Tj 1.244444 0 Td 50.231481 Tz (generated, ) Tj 3.130556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 58.333333 Tz (which ) Tj 1.886111 0 Td 53.472222 Tz (only ) Tj 1.497222 0 Td 55.092593 Tz (126 ) Tj 1.147222 0 Td 59.143519 Tz (were ) Tj 51.428571 0 0 51.428571 0 1126.742293 Tm 25.297222 0 Td 48.251029 Tz (available ) Tj 2.8 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 47.962963 Tz (biological ) Tj 3.130556 0 Td 44.486532 Tz (utilization ) Tj 3.130556 0 Td 58.333333 Tz (due ) Tj 1.244444 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 52.662037 Tz (presence ) Tj 2.722222 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 59.953704 Tz (an ) Tj 51.428571 0 0 51.428571 0 1085.307509 Tm 25.297222 0 Td 50.462963 Tz (anionic ) Tj 2.236111 0 Td 57.037037 Tz (group ) Tj 1.827778 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 50.854701 Tz (ionizationata ) Tj 4.063889 0 Td 54.012346 Tz (proper ) Tj 2.022222 0 Td 58.333333 Tz (pH. ) Tj 1.225 0 Td 63.194444 Tz (From ) Tj 1.652778 0 Td 43.75 Tz (this ) Tj 1.166667 0 Td 35.648148 Tz (list, ) Tj 1.244444 0 Td 56.17284 Tz (102 ) Tj 51.428571 0 0 51.428571 0 1042.622642 Tm 25.297222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 51.203704 Tz (those ) Tj 1.672222 0 Td 61.934156 Tz (compounds ) Tj 3.5 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 48.611111 Tz (available ) Tj 2.780556 0 Td 47.530864 Tz (for ) Tj 0.972222 0 Td 47.222222 Tz (further ) Tj 2.080556 0 Td 50.05144 Tz (autotaxin ) Tj 2.838889 0 Td 57.523148 Tz (inhi ) Tj 51.428571 0 0 51.428571 0 1001.03632 Tm 25.277778 0 Td 46.734893 Tz (bition/inactivation ) Tj 5.561111 0 Td 43.344907 Tz (testing. ) Tj 2.313889 0 Td 63.734568 Tz (The ) Tj 1.380556 0 Td 42.12963 Tz (final ) Tj 1.536111 0 Td 51.353276 Tz (determination ) Tj 4.238889 0 Td 62.654321 Tz (was ) Tj 1.361111 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 959.73957 Tm 25.297222 0 Td 72.376543 Tz (27% ) Tj 1.594444 0 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1.069444 0 Td 61.574074 Tz (poten ) Tj 51.428571 0 0 51.428571 0 836.837709 Tm 25.277778 0 Td 38.888889 Tz (tial ) Tj 1.088889 0 Td 56.565657 Tz (development ) Tj 3.869444 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 44.398148 Tz (relatively ) Tj 2.838889 0 Td 47.314815 Tz (large ) Tj 1.594444 0 Td 61.574074 Tz (number ) Tj 2.313889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 47.395833 Tz (suitable ) Tj 2.372222 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 796.361809 Tm 25.297222 0 Td 47.314815 Tz (inhibiting ) Tj 3.111111 0 Td 61.934156 Tz (compounds ) Tj 3.636111 0 Td 53.703704 Tz (through ) Tj 2.566667 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 51.851852 Tz (small ) Tj 1.866667 0 Td 64.814815 Tz (modicum ) Tj 3.033333 0 Td 56.712963 Tz (of ) Tj 0.875 0 Td 48.611111 Tz (actual ) Tj 51.428571 0 0 51.428571 0 751.795122 Tm 25.277778 0 Td 55.092593 Tz (time ) Tj 1.477778 0 Td 60.493827 Tz (and ) Tj 1.283333 0 Td 48.611111 Tz (resources, ) Tj 3.111111 0 Td 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462.588875 Tm 25.297222 0 Td 46.990741 Tz (orally ) Tj 1.866667 0 Td 49.259259 Tz (ingestable ) Tj 3.111111 0 Td 58.333333 Tz (form ) Tj 1.594444 0 Td 38.888889 Tz (is ) Tj 0.622222 0 Td 47.530864 Tz (possible. ) Tj 2.722222 0 Td 54.282407 Tz (This ) Tj 1.516667 0 Td 36.458333 Tz (list ) Tj 1.030556 0 Td 48.251029 Tz (includes, ) Tj 2.8 0 Td 52.777778 Tz (without ) Tj 51.428571 0 0 51.428571 0 421.34 Tm 25.297222 0 Td 45.37037 Tz (limitation, ) Tj 3.325 0 Td 44.965278 Tz (liquids, ) Tj 2.488889 0 Td 46.990741 Tz (liquid ) Tj 2.002778 0 Td 48.971193 Tz (capsules, ) Tj 2.936111 0 Td 43.75 Tz (tablets, ) Tj 2.430556 0 Td 52.391975 Tz (coated ) Tj 2.177778 0 Td 43.344907 Tz (tablets, ) Tj 51.428571 0 0 51.428571 0 377.218863 Tm 25.297222 0 Td 46.990741 Tz (minitablets, ) Tj 3.558333 0 Td 51.041667 Tz (capsules ) Tj 2.625 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 47.962963 Tz (individual ) Tj 3.052778 0 Td 50.771605 Tz (beads, ) Tj 1.944444 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 49.691358 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0.602778 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 44.290123 Tz (4\), ) Tj 1.05 0 Td 60.493827 Tz (two ) Tj 1.341667 0 Td 53.472222 Tz (aromatic ) Tj 51.428571 0 0 51.428571 0 2318.441982 Tm 6.358333 0 Td 56.388889 Tz (group ) Tj 1.983333 0 Td 50.05144 Tz (functions ) Tj 2.994444 0 Td 47.685185 Tz (\(points ) Tj 2.275 0 Td 58.333333 Tz (3 ) Tj 0.661111 0 Td 59.41358 Tz (and ) Tj 1.361111 0 Td 42.12963 Tz (5\), ) Tj 1.05 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 58.333333 Tz (one ) Tj 1.322222 0 Td 56.712963 Tz (hydrogen ) Tj 2.994444 0 Td 63.194444 Tz (bond ) Tj 51.428571 0 0 51.428571 0 2273.100295 Tm 6.358333 0 Td 57.685185 Tz (donor ) Tj 1.905556 0 Td 49.826389 Tz (function ) Tj 2.605556 0 Td 48.070988 Tz (\(point ) Tj 1.925 0 Td 41.049383 Tz (6\). ) Tj 38.571429 0 0 38.571429 0 2173 Tm 10.292593 0 Td 97.762346 Tz (DETAILED ) Tj 4.977778 0 Td 94.668911 Tz (DESCRIPTION ) Tj 6.533333 0 Td 99.382716 Tz (OF ) Tj 1.4 0 Td 106.584362 Tz (THE ) Tj 2.177778 0 Td 109.876543 Tz (DRAWING ) Tj 38.571429 0 0 38.571429 0 2129 Tm 12.262963 0 Td 116.666667 Tz (AND ) Tj 2.411111 0 Td 96.982167 Tz (INVENTION ) Tj 5.496296 0 Td 115.226337 Tz (AND ) Tj 2.359259 0 Td 100.823045 Tz (PREFERRED ) Tj 38.571429 0 0 38.571429 0 2086 Tm 16.592593 0 Td 107.239057 Tz (EMBODIMENTS ) Tj 51.428571 0 0 51.428571 0 1982.538259 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.361111 0 Td 45.775463 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 53.472222 Tz (below, ) Tj 2.177778 0 Td 48.611111 Tz (as ) Tj 0.836111 0 Td 51.851852 Tz (well ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 52.211934 Tz (following ) Tj 51.428571 0 0 51.428571 0 1939.46181 Tm 6.358333 0 Td 51.851852 Tz (exemplified ) Tj 3.558333 0 Td 57.87037 Tz (methods ) Tj 2.586111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 54.73251 Tz (producing ) Tj 3.072222 0 Td 52.5 Tz (using ) Tj 1.730556 0 Td 53.472222 Tz (Such ) Tj 1.438889 0 Td 61.934156 Tz (compounds ) Tj 3.480556 0 Td 49.691358 Tz (are ) Tj 51.428571 0 0 51.428571 0 1893.129187 Tm 6.358333 0 Td 50.771605 Tz (non-limiting ) Tj 3.791667 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (nature ) Tj 1.905556 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 49.691358 Tz (are ) Tj 1.030556 0 Td 50.231481 Tz (thus ) Tj 1.380556 0 Td 47.314815 Tz (indicative ) Tj 2.975 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 50.05144 Tz (preferred ) Tj 40 0 0 40 0 1855 Tm 8.175 0 Td 76.136364 Tz (embodiments ) Tj 5.3 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 56.25 Tz (this ) Tj 1.625 0 Td 60.833333 Tz (invention. ) Tj 48.571429 0 0 48.571429 0 1793 Tm 7.514706 0 Td 70.343137 Tz (As ) Tj 0.988235 0 Td 56.27451 Tz (noted ) Tj 1.791176 0 Td 56.045752 Tz (above, ) Tj 2.161765 0 Td 45.465686 Tz (this ) Tj 1.235294 0 Td 52.614379 Tz (invention ) Tj 2.985294 0 Td 41.176471 Tz (is ) Tj 0.658824 0 Td 51.470588 Tz (directed ) Tj 2.552941 0 Td 51.470588 Tz (to ) Tj 0.741176 0 Td 58.333333 Tz (a ) Tj 0.494118 0 Td 55.588235 Tz (novel ) Tj 1.811765 0 Td 64.624183 Tz (method ) Tj 51.428571 0 0 51.428571 0 1752.273796 Tm 6.358333 0 Td 56.712963 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (treating ) Tj 2.372222 0 Td 47.800926 Tz (patients ) Tj 2.469444 0 Td 52.662037 Tz (with ) Tj 1.419444 0 Td 47.395833 Tz (Suitable ) Tj 2.372222 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 47.638889 Tz (inhibiting ) Tj 2.994444 0 Td 58.333333 Tz (compounds. ) Tj 51.428571 0 0 51.428571 0 1706.491272 Tm 6.377778 0 Td 59.143519 Tz (Such ) Tj 1.672222 0 Td 62.294239 Tz (compounds ) Tj 3.636111 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 54.444444 Tz (determined ) Tj 3.558333 0 Td 52.777778 Tz (through ) Tj 2.469444 0 Td 55.092593 Tz (a ) Tj 0.602778 0 Td 51.041667 Tz (very ) Tj 1.516667 0 Td 43.930041 Tz (efficient ) Tj 51.428571 0 0 51.428571 0 1664.716418 Tm 6.377778 0 Td 51.49177 Tz (screening ) Tj 2.994444 0 Td 51.527778 Tz (procedure, ) Tj 3.325 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 46.018519 Tz (exist ) Tj 1.575 0 Td 51.851852 Tz (as ) Tj 0.875 0 Td 50.231481 Tz (lead ) Tj 1.419444 0 Td 61.934156 Tz (compounds ) Tj 3.597222 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 52.857143 0 0 52.857143 0 1619.874693 Tm 6.186486 0 Td 45.895896 Tz (potential ) Tj 2.686486 0 Td 47.297297 Tz (to ) Tj 0.775676 0 Td 43.513514 Tz (treat ) Tj 1.532432 0 Td 46.150696 Tz (metastasis, ) Tj 3.291892 0 Td 45.326577 Tz (obesity, ) Tj 2.440541 0 Td 50.1638 Tz (neuropathic ) Tj 3.518919 0 Td 47.297297 Tz (pain, ) Tj 1.645946 0 Td 60.960961 Tz (ath ) Tj 48.571429 0 0 48.571429 0 1573 Tm 6.732353 0 Td 50.326797 Tz (erosclerosis ) Tj 3.788235 0 Td 62.908497 Tz (and ) Tj 1.317647 0 Td 58.333333 Tz (rheumatoid ) Tj 3.644118 0 Td 43.578431 Tz (arthritis, ) Tj 2.779412 0 Td 46.323529 Tz (at ) Tj 0.761765 0 Td 43.464052 Tz (least, ) Tj 1.75 0 Td 53.75817 Tz (within ) Tj 2.141176 0 Td 54.901961 Tz (a ) Tj 0.555882 0 Td 97.222222 Tz (mam ) Tj 51.428571 0 0 51.428571 0 1528.85906 Tm 6.358333 0 Td 55.092593 Tz (malian ) Tj 2.411111 0 Td 51.851852 Tz (body. ) Tj 1.963889 0 Td 66.435185 Tz (As ) Tj 1.225 0 Td 51.851852 Tz (described ) Tj 3.188889 0 Td 52.932099 Tz (above, ) Tj 2.352778 0 Td 48.611111 Tz (the ) Tj 1.283333 0 Td 50.05144 Tz (autotaxin ) Tj 3.169444 0 Td 62.222222 Tz (\(ATX\) ) Tj 51.428571 0 0 51.428571 0 1487.755869 Tm 6.358333 0 Td 63.194444 Tz (enzyme ) Tj 2.391667 0 Td 56.30787 Tz (promotes ) Tj 2.838889 0 Td 43.75 Tz (cell ) Tj 1.205556 0 Td 51.851852 Tz (migration ) Tj 2.916667 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 47.890947 Tz (invasion, ) Tj 2.702778 0 Td 50.231481 Tz (thus ) Tj 1.361111 0 Td 47.638889 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1441.54933 Tm 6.358333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 77.777778 Tz (ATX ) Tj 1.555556 0 Td 40.509259 Tz (is ) Tj 0.641667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 52.5 Tz (value ) Tj 1.730556 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 51.527778 Tz (prevention ) Tj 3.286111 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 49.259259 Tz (metastasis ) Tj 3.130556 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 51.851852 Tz (other ) Tj 51.428571 0 0 51.428571 0 1400.440633 Tm 6.358333 0 Td 53.877315 Tz (maladies ) Tj 2.780556 0 Td 53.796296 Tz (noted ) Tj 1.788889 0 Td 48.021886 Tz (previously. ) Tj 51.428571 0 0 51.428571 0 1346.516883 Tm 7.116667 0 Td 46.990741 Tz (In ) Tj 0.797222 0 Td 53.796296 Tz (terms ) Tj 1.866667 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 51.851852 Tz (screening ) Tj 2.994444 0 Td 51.851852 Tz (procedure, ) Tj 3.344444 0 Td 41.409465 Tz (initially ) Tj 2.488889 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 51.851852 Tz (process ) Tj 51.428571 0 0 51.428571 0 1301.881188 Tm 6.358333 0 Td 51.851852 Tz (involved ) Tj 2.761111 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 51.527778 Tz (generation ) Tj 3.383333 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 54.012346 Tz (proper ) Tj 2.197222 0 Td 58.333333 Tz (pharmacophore ) Tj 4.822222 0 Td 56.388889 Tz (based ) Tj 51.428571 0 0 51.428571 0 1254.881748 Tm 6.338889 0 Td 60.763889 Tz (upon ) Tj 1.827778 0 Td 48.611111 Tz (the ) Tj 1.244444 0 Td 46.342593 Tz (structures ) Tj 3.130556 0 Td 59.953704 Tz (of ) Tj 0.952778 0 Td 50 Tz (already ) Tj 2.488889 0 Td 64.814815 Tz (known ) Tj 2.294444 0 Td 46.450617 Tz (effective ) Tj 2.838889 0 Td 50.771605 Tz (autotaxin ) Tj 51.428571 0 0 51.428571 0 1216.745679 Tm 6.358333 0 Td 47.314815 Tz (inhibiting ) Tj 3.052778 0 Td 58.657407 Tz (compounds. ) Tj 3.811111 0 Td 53.472222 Tz (FIG. ) Tj 1.575 0 Td 45.37037 Tz (1 ) Tj 0.563889 0 Td 51.446759 Tz (provides ) Tj 2.702778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.311728 Tz (parent ) Tj 2.061111 0 Td 48.251029 Tz (six-point ) Tj 51.428571 0 0 51.428571 0 1172.548926 Tm 6.358333 0 Td 58.084046 Tz (pharmacophore ) Tj 4.725 0 Td 52.211934 Tz (generated ) Tj 2.994444 0 Td 55.740741 Tz (based ) Tj 1.866667 0 Td 59.953704 Tz (upon ) Tj 1.633333 0 Td 56.388889 Tz (comparison ) Tj 3.597222 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 64.814815 Tz (pre ) Tj 51.428571 0 0 51.428571 0 1128.5 Tm 6.358333 0 Td 50.925926 Tz (viously ) Tj 2.45 0 Td 59.41358 Tz (known, ) Tj 2.469444 0 Td 50.87963 Tz (acceptable ) Tj 3.344444 0 Td 77.777778 Tz (ATX ) Tj 1.730556 0 Td 44.486532 Tz (inhibitors. ) Tj 3.266667 0 Td 45.619658 Tz (Specifically, ) Tj 3.888889 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1086.648949 Tm 6.358333 0 Td 47.962963 Tz (large ) Tj 1.633333 0 Td 50.462963 Tz (anionic ) Tj 2.294444 0 Td 57.037037 Tz (group ) Tj 1.925 0 Td 49.826389 Tz (function ) Tj 2.625 0 Td 56.712963 Tz (must ) Tj 1.555556 0 Td 58.333333 Tz (be ) Tj 0.855556 0 Td 50 Tz (present ) Tj 2.313889 0 Td 46.450617 Tz (for ) Tj 1.011111 0 Td 53.472222 Tz (proper ) Tj 2.1 0 Td 63.734568 Tz (ion ) Tj 51.428571 0 0 51.428571 0 1045.108374 Tm 6.358333 0 Td 46.759259 Tz (ization ) Tj 2.138889 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 48.611111 Tz (biological ) Tj 3.091667 0 Td 72.916667 Tz (pH ) Tj 1.069444 0 Td 42.669753 Tz (level; ) Tj 1.711111 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.851852 Tz (metal ) Tj 1.730556 0 Td 45.37037 Tz (ligators ) Tj 2.313889 0 Td 50.925926 Tz (present ) Tj 2.313889 0 Td 45.37037 Tz (\(as ) Tj 51.428571 0 0 51.428571 0 1003.014085 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.711111 0 Td 55.092593 Tz (above\) ) Tj 2.080556 0 Td 55.092593 Tz (coupled ) Tj 2.430556 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 50.771605 Tz (the ) Tj 0.972222 0 Td 53.472222 Tz (aromatic ) Tj 2.663889 0 Td 55.632716 Tz (groups ) Tj 2.1 0 Td 59.41358 Tz (and ) Tj 1.166667 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 64.166667 Tz (hydro ) Tj 51.428571 0 0 51.428571 0 958.520245 Tm 6.358333 0 Td 57.253086 Tz (gen ) Tj 1.205556 0 Td 60.763889 Tz (bond ) Tj 1.613889 0 Td 51.311728 Tz (donor, ) Tj 2.002778 0 Td 39.969136 Tz (all ) Tj 0.875 0 Td 49.259259 Tz (contribute ) Tj 3.091667 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 64.00463 Tz (some ) Tj 1.672222 0 Td 50.925926 Tz (fashion ) Tj 2.294444 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 51.851852 Tz (reactiv ) Tj 51.428571 0 0 51.428571 0 921.363636 Tm 6.358333 0 Td 42.12963 Tz (ity ) Tj 0.972222 0 Td 51.851852 Tz (necessary ) Tj 3.013889 0 Td 52.662037 Tz (with ) Tj 1.458333 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 48.611111 Tz (large ) Tj 1.594444 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 58.333333 Tz (enzyme. ) Tj 2.625 0 Td 66.435185 Tz (As ) Tj 0.991667 0 Td 51.851852 Tz (discussed ) Tj 2.975 0 Td 64.814815 Tz (pre ) Tj 51.428571 0 0 51.428571 0 880.597964 Tm 6.358333 0 Td 47.395833 Tz (viously, ) Tj 2.663889 0 Td 53.877315 Tz (however, ) Tj 2.955556 0 Td 43.75 Tz (this ) Tj 1.419444 0 Td 51.851852 Tz (parent ) Tj 2.216667 0 Td 58.084046 Tz (pharmacophore ) Tj 4.880556 0 Td 56.17284 Tz (proved ) Tj 2.372222 0 Td 52.932099 Tz (too ) Tj 51.428571 0 0 51.428571 0 835.43 Tm 6.358333 0 Td 43.897306 Tz (restrictive ) Tj 3.227778 0 Td 43.75 Tz (to ) Tj 0.855556 0 Td 54.012346 Tz (determine ) Tj 3.227778 0 Td 57.253086 Tz (any ) Tj 1.361111 0 Td 48.316498 Tz (discernible ) Tj 3.480556 0 Td 55.976431 Tz (comparisons ) Tj 4.044444 0 Td 54.282407 Tz (with ) Tj 51.428571 0 0 51.428571 0 794.526829 Tm 6.358333 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 49.259259 Tz (databases; ) Tj 3.188889 0 Td 56.712963 Tz (no ) Tj 0.855556 0 Td 54.552469 Tz (proper ) Tj 2.1 0 Td 43.75 Tz (hits ) Tj 1.244444 0 Td 59.143519 Tz (were ) Tj 1.594444 0 Td 51.851852 Tz (found, ) Tj 2.061111 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 49.421296 Tz (essence. ) Tj 51.428571 0 0 51.428571 0 754.784409 Tm 6.358333 0 Td 53.472222 Tz (This ) Tj 1.497222 0 Td 49.691358 Tz (led ) Tj 1.05 0 Td 48.611111 Tz (to ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 53.472222 Tz (unexpectedly ) Tj 4.083333 0 Td 48.287037 Tz (Surprising ) Tj 3.111111 0 Td 44.830247 Tz (result ) Tj 1.769444 0 Td 46.990741 Tz (that ) Tj 1.302778 0 Td 58.333333 Tz (removing ) Tj 51.428571 0 0 51.428571 0 710.067416 Tm 6.358333 0 Td 59.41358 Tz (one ) Tj 1.341667 0 Td 55.092593 Tz (or ) Tj 0.913889 0 Td 58.333333 Tz (two ) Tj 1.341667 0 Td 61.574074 Tz (of ) Tj 0.913889 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 43.75 Tz (2, ) Tj 0.816667 0 Td 45.37037 Tz (3, ) Tj 0.836111 0 Td 45.37037 Tz (4, ) Tj 0.816667 0 Td 55.092593 Tz (or ) Tj 0.933333 0 Td 55.092593 Tz (5 ) Tj 0.641667 0 Td 50.05144 Tz (functions ) Tj 2.994444 0 Td 58.333333 Tz (from ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 51.311728 Tz (parent ) Tj 51.428571 0 0 51.428571 0 672.492253 Tm 6.358333 0 Td 58.084046 Tz (pharmacophore ) Tj 4.686111 0 Td 55.497685 Tz (accorded ) Tj 2.819444 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 58.333333 Tz (5 ) Tj 0.544444 0 Td 53.472222 Tz (or ) Tj 0.777778 0 Td 50.925926 Tz (4-point ) Tj 2.313889 0 Td 58.084046 Tz (pharmacophore ) Tj 4.705556 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 629.461929 Tm 6.358333 0 Td 51.851852 Tz (permitted ) Tj 3.111111 0 Td 47.685185 Tz (further ) Tj 2.294444 0 Td 53.20216 Tz (comparisons. ) Tj 4.180556 0 Td 57.523148 Tz (With ) Tj 1.711111 0 Td 51.851852 Tz (a ) Tj 0.641667 0 Td 49.537037 Tz (limited ) Tj 2.411111 0 Td 61.574074 Tz (number ) Tj 2.508333 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 588.269377 Tm 6.358333 0 Td 54.208754 Tz (comparative ) Tj 3.927778 0 Td 55.092593 Tz (base ) Tj 1.691667 0 Td 50.555556 Tz (point ) Tj 1.886111 0 Td 47.638889 Tz (functions, ) Tj 3.247222 0 Td 51.203704 Tz (generation ) Tj 3.480556 0 Td 56.712963 Tz (of ) Tj 0.972222 0 Td 47.395833 Tz (Suitable ) Tj 51.428571 0 0 51.428571 0 545.112195 Tm 6.358333 0 Td 44.907407 Tz (results ) Tj 2.119444 0 Td 43.75 Tz (in ) Tj 0.758333 0 Td 53.148148 Tz (terms ) Tj 1.788889 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 46.450617 Tz (effective ) Tj 2.683333 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 47.314815 Tz (inhibiting ) Tj 3.013889 0 Td 62.294239 Tz (compounds ) Tj 3.577778 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 502.34767 Tm 6.358333 0 Td 52.932099 Tz (not ) Tj 1.069444 0 Td 50.771605 Tz (expected. ) Tj 2.955556 0 Td 56.712963 Tz (However, ) Tj 2.877778 0 Td 46.990741 Tz (in ) Tj 0.719444 0 Td 51.851852 Tz (order ) Tj 1.672222 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 47.685185 Tz (further ) Tj 2.119444 0 Td 54.012346 Tz (determine ) Tj 3.072222 0 Td 46.990741 Tz (suitable ) Tj 51.428571 0 0 51.428571 0 462.547912 Tm 6.358333 0 Td 58.981481 Tz (compounds, ) Tj 3.733333 0 Td 34.027778 Tz (it ) Tj 0.602778 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 54.166667 Tz (decided ) Tj 2.469444 0 Td 43.75 Tz (to ) Tj 0.758333 0 Td 55.092593 Tz (narrow ) Tj 2.197222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 44.622507 Tz (possibilities ) Tj 3.655556 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 422.160389 Tm 6.358333 0 Td 54.73251 Tz (remaining ) Tj 3.111111 0 Td 55.092593 Tz (base ) Tj 1.497222 0 Td 50.555556 Tz (point ) Tj 1.711111 0 Td 49.826389 Tz (function ) Tj 2.605556 0 Td 53.472222 Tz (comparisons, ) Tj 4.044444 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 53.796296 Tz (terms ) Tj 1.827778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 62.654321 Tz (Vol ) Tj 48.571429 0 0 48.571429 0 378 Tm 6.711765 0 Td 68.627451 Tz (umes ) Tj 2.038235 0 Td 62.908497 Tz (and ) Tj 1.523529 0 Td 51.851852 Tz (distances ) Tj 3.211765 0 Td 55.165913 Tz (therebetween, ) Tj 4.735294 0 Td 46.323529 Tz (in ) Tj 0.947059 0 Td 53.186275 Tz (essence, ) Tj 2.964706 0 Td 46.323529 Tz (to ) Tj 1.008824 0 Td 50.490196 Tz (certain ) Tj 51.428571 0 0 51.428571 0 337.724221 Tm 6.358333 0 Td 52.391975 Tz (ranges ) Tj 2.022222 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 43.287037 Tz (possibilities. ) Tj 3.772222 0 Td 52.5 Tz (Table ) Tj 1.788889 0 Td 40.509259 Tz (1, ) Tj 0.602778 0 Td 52.932099 Tz (below, ) Tj 2.041667 0 Td 59.62963 Tz (shows ) Tj 1.925 0 Td 39.969136 Tz (all ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 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(results, ) Tj 2.177778 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 61.574074 Tz (number ) Tj 2.313889 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 53.914141 Tz (comparative ) Tj 3.675 0 Td 42.939815 Tz (hits ) Tj 1.186111 0 Td 55.555556 Tz (meeting ) Tj 40 0 0 40 0 2875 Tm 8.15 0 Td 65 Tz (these ) Tj 2.35 0 Td 54.166667 Tz (critical ) Tj 3.075 0 Td 73.611111 Tz (measurements ) Tj 5.725 0 Td 76.041667 Tz (were ) Tj 2.225 0 Td 64.880952 Tz (located ) Tj 3.125 0 Td 65.972222 Tz (within ) Tj 2.825 0 Td 63.888889 Tz (the ) Tj 1.55 0 Td 88.888889 Tz (NCI ) Tj 51.428571 0 0 51.428571 0 2824.959811 Tm 6.358333 0 Td 49.331276 Tz (database. ) Tj 2.8 0 Td 51.851852 Tz (After ) Tj 1.652778 0 Td 51.131687 Tz (acquiring ) Tj 2.916667 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 61.574074 Tz (compounds ) Tj 3.480556 0 Td 46.180556 Tz (that ) Tj 1.263889 0 Td 57.523148 Tz (were ) Tj 1.555556 0 Td 46.018519 Tz (identified ) Tj 51.428571 0 0 51.428571 0 2779.862722 Tm 6.358333 0 Td 58.333333 Tz (from ) Tj 1.516667 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 58.333333 Tz (pharmacophore ) Tj 4.666667 0 Td 48.251029 Tz (searches, ) Tj 2.741667 0 Td 58.333333 Tz (a ) Tj 0.466667 0 Td 56.388889 Tz (comparison ) Tj 3.538889 0 Td 61.574074 Tz (was ) Tj 1.283333 0 Td 64.00463 Tz (made ) Tj 1.672222 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 2732.270833 Tm 6.358333 0 Td 52.5 Tz (order ) Tj 1.827778 0 Td 45.37037 Tz (to ) Tj 0.816667 0 Td 46.990741 Tz (identify ) Tj 2.527778 0 Td 41.049383 Tz (all ) Tj 1.030556 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 55.092593 Tz (unique ) Tj 2.236111 0 Td 46.990741 Tz (structures ) Tj 3.130556 0 Td 57.523148 Tz (from ) Tj 1.691667 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 44.444444 Tz (virtual ) Tj 51.428571 0 0 51.428571 0 2686.924183 Tm 6.377778 0 Td 47.685185 Tz (screen. ) Tj 2.294444 0 Td 53.796296 Tz (Table ) Tj 1.905556 0 Td 51.851852 Tz (2 ) Tj 0.622222 0 Td 59.62963 Tz (shows ) Tj 2.1 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 54.208754 Tz (comparative ) Tj 3.869444 0 Td 44.444444 Tz (results ) Tj 2.197222 0 Td 50.231481 Tz (then ) Tj 1.497222 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2643.588045 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.538889 0 Td 50 Tz (located ) Tj 2.294444 0 Td 57.523148 Tz (from ) Tj 1.594444 0 Td 54.282407 Tz (Such ) Tj 1.477778 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 53.914141 Tz (comparison. ) Tj 38.571429 0 0 38.571429 0 2555 Tm 18.251852 0 Td 101.111111 Tz (TABLE ) Tj 3.266667 0 Td 77.777778 Tz (2 ) Tj 41.428571 0 0 41.428571 0 2484.461538 Tm 14.217241 0 Td 49.616858 Tz (Hit ) Tj 1.062069 0 Td 52.664577 Tz (acquirement ) Tj 3.644828 0 Td 56.321839 Tz (and ) Tj 1.231034 0 Td 46.812957 Tz (refinement. ) Tj 40 0 0 40 0 2418.931459 Tm 13.475 0 Td 68.055556 Tz (Number ) Tj 2.625 0 Td 54.166667 Tz (of ) Tj 1.075 0 Td 50 Tz (Total ) Tj 1.7 0 Td 59.027778 Tz (Unique ) Tj 2.8 0 Td 59.027778 Tz (Unique ) Tj 2.35 0 Td 49.537037 Tz (Ionizable ) Tj 3.55 0 Td 56.25 Tz (Acquired ) Tj 33.142857 0 0 33.142857 0 2389 Tm 9.866379 0 Td 70.789125 Tz (Pharmacophore ) Tj 7.663793 0 Td 59.087644 Tz (Hits ) Tj 4.827586 0 Td 59.087644 Tz (Hits ) Tj 6.155172 0 Td 57.83046 Tz (Hits ) Tj 5.702586 0 Td 57.83046 Tz (Hits ) Tj 30 0 0 30 0 2328 Tm 10.866667 0 Td 80.555556 Tz (4a ) Tj 8.833333 0 Td 72.222222 Tz (13 ) Tj 5.1 0 Td 75.925926 Tz (160 ) Tj 6.8 0 Td 75.925926 Tz (126 ) Tj 6.3 0 Td 75.925926 Tz (102 ) Tj 30.714286 0 0 30.714286 0 2294 Tm 10.613953 0 Td 81.395349 Tz (4b ) Tj 8.562791 0 Td 73.255814 Tz (31 ) Tj 30 0 0 30 0 2261 Tm 10.866667 0 Td 80.555556 Tz (4c ) Tj 8.766667 0 Td 75 Tz (71 ) Tj 30.714286 0 0 30.714286 0 2228 Tm 10.613953 0 Td 84.108527 Tz (4d ) Tj 8.562791 0 Td 73.255814 Tz (71 ) Tj 30 0 0 30 0 2195 Tm 10.966667 0 Td 66.666667 Tz (Sa ) Tj 9.2 0 Td 72.222222 Tz (8 ) Tj 30.714286 0 0 30.714286 0 2161 Tm 10.711628 0 Td 73.255814 Tz (Sb ) Tj 8.465116 0 Td 75.968992 Tz (35 ) Tj 30 0 0 30 0 2128 Tm 10.9 0 Td 77.777778 Tz (Sc ) Tj 9.233333 0 Td 72.222222 Tz (3 ) Tj 30.714286 0 0 30.714286 0 2095 Tm 10.646512 0 Td 75.968992 Tz (Sd ) Tj 8.530233 0 Td 73.255814 Tz (21 ) Tj 30 0 0 30 0 2062 Tm 10.933333 0 Td 72.222222 Tz (6 ) Tj 9.266667 0 Td 55.555556 Tz (1 ) Tj 51.428571 0 0 51.428571 0 1955.33584 Tm 7.097222 0 Td 71.296296 Tz (Of ) Tj 0.933333 0 Td 59.41358 Tz (254 ) Tj 1.244444 0 Td 43.425926 Tz (total ) Tj 1.497222 0 Td 46.666667 Tz (structures ) Tj 2.994444 0 Td 45.37037 Tz (identified ) Tj 2.916667 0 Td 56.712963 Tz (from ) Tj 1.575 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 58.084046 Tz (pharmacophore ) Tj 51.428571 0 0 51.428571 0 1909.862745 Tm 6.377778 0 Td 48.251029 Tz (searches, ) Tj 2.877778 0 Td 57.253086 Tz (160 ) Tj 1.166667 0 Td 59.953704 Tz (were ) Tj 1.575 0 Td 50.925926 Tz (unique. ) Tj 2.372222 0 Td 63.194444 Tz (From ) Tj 1.730556 0 Td 50.555556 Tz (those ) Tj 1.75 0 Td 58.333333 Tz (160 ) Tj 1.166667 0 Td 58.981481 Tz (compounds, ) Tj 3.772222 0 Td 57.253086 Tz (126 ) Tj 51.428571 0 0 51.428571 0 1866.263905 Tm 6.358333 0 Td 47.800926 Tz (actually ) Tj 2.469444 0 Td 60.277778 Tz (would ) Tj 1.944444 0 Td 49.691358 Tz (ionize ) Tj 1.925 0 Td 45.37037 Tz (at ) Tj 0.661111 0 Td 48.611111 Tz (biological ) Tj 3.072222 0 Td 59.41358 Tz (pH, ) Tj 1.244444 0 Td 49.259259 Tz (since ) Tj 1.633333 0 Td 58.084046 Tz (pharmacophore ) Tj 51.428571 0 0 51.428571 0 1817.799486 Tm 6.358333 0 Td 50.555556 Tz (point ) Tj 1.769444 0 Td 35.648148 Tz (1 ) Tj 0.505556 0 Td 40.509259 Tz (is ) Tj 0.7 0 Td 55.092593 Tz (an ) Tj 0.875 0 Td 50.925926 Tz (anionic ) Tj 2.372222 0 Td 48.935185 Tz (functional ) Tj 3.130556 0 Td 52.391975 Tz (group. ) Tj 2.080556 0 Td 66.435185 Tz (As ) Tj 1.030556 0 Td 53.148148 Tz (noted ) Tj 1.808333 0 Td 52.391975 Tz (above, ) Tj 2.158333 0 Td 56.17284 Tz (102 ) Tj 51.428571 0 0 51.428571 0 1773.235955 Tm 6.358333 0 Td 52.932099 Tz (out ) Tj 1.166667 0 Td 55.092593 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 54.73251 Tz (remaining ) Tj 3.227778 0 Td 56.17284 Tz (126 ) Tj 1.244444 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 49.691358 Tz (ere ) Tj 1.108333 0 Td 51.041667 Tz (then ) Tj 1.438889 0 Td 44.444444 Tz (tested. ) Tj 2.080556 0 Td 58.981481 Tz (These ) Tj 51.428571 0 0 51.428571 0 1728.290398 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.5 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 51.851852 Tz (then ) Tj 1.361111 0 Td 53.877315 Tz (analyzed ) Tj 2.722222 0 Td 47.530864 Tz (for ) Tj 0.952778 0 Td 75.617284 Tz (ATX ) Tj 1.477778 0 Td 47.314815 Tz (inhibition ) Tj 2.955556 0 Td 45.075758 Tz (capability, ) Tj 40 0 0 40 0 1686 Tm 8.175 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 66.203704 Tz (described ) Tj 3.775 0 Td 67.361111 Tz (below. ) Tj 52.857143 0 0 52.857143 0 1634.366559 Tm 6.186486 0 Td 76.726727 Tz (ATX ) Tj 1.589189 0 Td 46.036036 Tz (Inhibition ) Tj 2.894595 0 Td 58.018018 Tz (Assay ) Tj 51.428571 0 0 51.428571 0 1587.992528 Tm 7.097222 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 46.990741 Tz (inhibition ) Tj 2.955556 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 54.166667 Tz (assayed ) Tj 2.391667 0 Td 53.796296 Tz (using ) Tj 1.730556 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 48.251029 Tz (substrate ) Tj 2.761111 0 Td 55.092593 Tz (FS-3 ) Tj 1.516667 0 Td 66.435185 Tz (\(Ech ) Tj 51.428571 0 0 51.428571 0 1540.708738 Tm 6.358333 0 Td 51.851852 Tz (elon ) Tj 1.458333 0 Td 49.96142 Tz (Biosciences, ) Tj 3.752778 0 Td 42.12963 Tz (Inc., ) Tj 1.419444 0 Td 47.800926 Tz (Salt ) Tj 1.322222 0 Td 59.143519 Tz (Lake ) Tj 1.516667 0 Td 47.314815 Tz (City, ) Tj 1.555556 0 Td 53.148148 Tz (Utah, ) Tj 1.75 0 Td 61.574074 Tz (USA\). ) Tj 2.002778 0 Td 62.654321 Tz (The ) Tj 1.302778 0 Td 56.712963 Tz (FS-3 ) Tj 51.428571 0 0 51.428571 0 1494.787208 Tm 6.358333 0 Td 51.851852 Tz (assay ) Tj 1.827778 0 Td 55.902778 Tz (used ) Tj 1.652778 0 Td 60.493827 Tz (~10 ) Tj 1.341667 0 Td 51.851852 Tz (times ) Tj 1.847222 0 Td 51.311728 Tz (concentrated ) Tj 3.966667 0 Td 51.557239 Tz (conditioned ) Tj 3.675 0 Td 52.824074 Tz (serum-free ) Tj 51.428571 0 0 51.428571 0 1449 Tm 6.358333 0 Td 65.895062 Tz (medium ) Tj 2.625 0 Td 69.351852 Tz (\(CCM\) ) Tj 2.333333 0 Td 57.523148 Tz (from ) Tj 1.633333 0 Td 72.916667 Tz (MDA-MB-435 ) Tj 4.608333 0 Td 44.074074 Tz (cells ) Tj 1.555556 0 Td 48.611111 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 52.932099 Tz (source ) Tj 2.119444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1404.554455 Tm 6.358333 0 Td 66.435185 Tz (ATX, ) Tj 1.827778 0 Td 53.796296 Tz (while ) Tj 1.827778 0 Td 89.660494 Tz (CCM ) Tj 1.827778 0 Td 56.532922 Tz (comprised ) Tj 3.286111 0 Td 49.331276 Tz (one-third ) Tj 2.858333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 47.530864 Tz (the ) Tj 1.108333 0 Td 42.12963 Tz (total ) Tj 1.516667 0 Td 55.092593 Tz (volume. ) Tj 51.428571 0 0 51.428571 0 1358.548387 Tm 6.358333 0 Td 63.734568 Tz (The ) Tj 1.341667 0 Td 41.481481 Tz (final ) Tj 1.477778 0 Td 59.953704 Tz (volume ) Tj 2.333333 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 55.902778 Tz (FS-3 ) Tj 1.575 0 Td 60.493827 Tz (was ) Tj 1.302778 0 Td 56.17284 Tz (comprised ) Tj 3.188889 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 47.890947 Tz (substrate ) Tj 2.741667 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 1316.501901 Tm 6.358333 0 Td 53.240741 Tz (varying ) Tj 2.508333 0 Td 50.462963 Tz (concentrations ) Tj 4.530556 0 Td 60.493827 Tz (and ) Tj 1.380556 0 Td 61.574074 Tz (30 ) Tj 1.4 0 Td 106.944444 Tz (M ) Tj 0.972222 0 Td 49.56427 Tz (charcoal-stripped ) Tj 5.347222 0 Td 44.722222 Tz (fatty ) Tj 51.428571 0 0 51.428571 0 1267.933842 Tm 6.358333 0 Td 51.041667 Tz (acid ) Tj 1.438889 0 Td 46.990741 Tz (free ) Tj 1.380556 0 Td 75.617284 Tz (BSA ) Tj 1.575 0 Td 58.333333 Tz (\(Sigma ) Tj 2.294444 0 Td 51.446759 Tz (Aldrich\) ) Tj 2.683333 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 53.148148 Tz (assay ) Tj 1.808333 0 Td 49.151235 Tz (buffer ) Tj 1.963889 0 Td 45.37037 Tz (\(1 ) Tj 0.855556 0 Td 97.222222 Tz (mM ) Tj 1.380556 0 Td 57.523148 Tz (each ) Tj 51.428571 0 0 51.428571 0 1221.546798 Tm 6.358333 0 Td 64.814815 Tz (CaCl ) Tj 1.905556 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 71.296296 Tz (MgCl, ) Tj 2.294444 0 Td 55.092593 Tz (5 ) Tj 0.486111 0 Td 75.07716 Tz (mMKC1, ) Tj 2.936111 0 Td 56.17284 Tz (140 ) Tj 1.147222 0 Td 72.222222 Tz (mMNaCl, ) Tj 3.188889 0 Td 59.953704 Tz (50 ) Tj 0.836111 0 Td 100.462963 Tz (mM ) Tj 1.322222 0 Td 46.990741 Tz (Tris ) Tj 1.244444 0 Td 76.157407 Tz (pH ) Tj 51.428571 0 0 51.428571 0 1174 Tm 6.377778 0 Td 42.777778 Tz (8.0\). ) Tj 51.428571 0 0 51.428571 0 1132.444444 Tm 7.097222 0 Td 50.771605 Tz (All ) Tj 1.05 0 Td 52.391975 Tz (assays ) Tj 2.022222 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 56.17284 Tz (performed ) Tj 3.188889 0 Td 45.37037 Tz (in ) Tj 0.680556 0 Td 53.240741 Tz (96-well ) Tj 2.352778 0 Td 47.530864 Tz (plates ) Tj 1.886111 0 Td 51.851852 Tz (with ) Tj 1.419444 0 Td 49.421296 Tz (data ) Tj 1.380556 0 Td 51.851852 Tz (read ) Tj 51.428571 0 0 51.428571 0 1086.243553 Tm 6.358333 0 Td 45.37037 Tz (at ) Tj 1.05 0 Td 38.888889 Tz (1 ) Tj 0.777778 0 Td 55.632716 Tz (minute ) Tj 2.469444 0 Td 45.730453 Tz (intervals ) Tj 2.916667 0 Td 61.574074 Tz (by ) Tj 1.205556 0 Td 51.851852 Tz (a ) Tj 0.797222 0 Td 57.523148 Tz (Synergy2 ) Tj 3.208333 0 Td 55.632716 Tz (system ) Tj 2.508333 0 Td 52.256944 Tz (\(BioTek, ) Tj 51.428571 0 0 51.428571 0 1040.198124 Tm 6.358333 0 Td 55.092593 Tz (Winooski, ) Tj 3.091667 0 Td 42.777778 Tz (Vt.\). ) Tj 1.419444 0 Td 63.734568 Tz (The ) Tj 1.263889 0 Td 50.231481 Tz (fluorescence ) Tj 3.752778 0 Td 56.712963 Tz (produced ) Tj 2.858333 0 Td 59.143519 Tz (upon ) Tj 1.536111 0 Td 51.851852 Tz (the ) Tj 1.05 0 Td 59.259259 Tz (hydroly ) Tj 51.428571 0 0 51.428571 0 993.445798 Tm 6.377778 0 Td 41.049383 Tz (sis ) Tj 0.913889 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 56.712963 Tz (FS-3 ) Tj 1.575 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 55.092593 Tz (monitored ) Tj 3.15 0 Td 52.5 Tz (using ) Tj 1.730556 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 47.314815 Tz (excitation ) Tj 3.033333 0 Td 55.092593 Tz (wavelength ) Tj 3.5 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 947.83378 Tm 6.358333 0 Td 60.493827 Tz (485 ) Tj 1.380556 0 Td 74.537037 Tz (nm ) Tj 1.186111 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 56.712963 Tz (an ) Tj 0.972222 0 Td 53.472222 Tz (emission ) Tj 2.858333 0 Td 55.416667 Tz (wavelength ) Tj 3.577778 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 60.493827 Tz (528 ) Tj 1.380556 0 Td 74.537037 Tz (nm ) Tj 1.166667 0 Td 45.37037 Tz (at ) Tj 0.797222 0 Td 56.17284 Tz (37 ) Tj 1.302778 0 Td 53.472222 Tz (C. ) Tj 51.428571 0 0 51.428571 0 901.589333 Tm 6.377778 0 Td 53.652263 Tz (\(Ferguson ) Tj 3.188889 0 Td 43.75 Tz (et ) Tj 0.797222 0 Td 37.268519 Tz (al., ) Tj 1.166667 0 Td 51.311728 Tz (2006\). ) Tj 2.216667 0 Td 48.611111 Tz (Results ) Tj 2.352778 0 Td 49.691358 Tz (are ) Tj 1.166667 0 Td 61.574074 Tz (shown ) Tj 2.158333 0 Td 43.75 Tz (at ) Tj 0.797222 0 Td 58.333333 Tz (one ) Tj 1.302778 0 Td 49.907407 Tz (hour, ) Tj 1.75 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 856.005089 Tm 6.338889 0 Td 59.62963 Tz (which ) Tj 2.061111 0 Td 50.555556 Tz (point ) Tj 1.769444 0 Td 41.049383 Tz (all ) Tj 1.030556 0 Td 50.501543 Tz (fluorescence ) Tj 3.908333 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 54.444444 Tz (absorbance ) Tj 3.558333 0 Td 55.092593 Tz (changes ) Tj 2.586111 0 Td 51.851852 Tz (as ) Tj 0.913889 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 810.196622 Tm 6.358333 0 Td 50.231481 Tz (function ) Tj 2.566667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.472222 Tz (time ) Tj 1.438889 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 42.592593 Tz (linear. ) Tj 1.925 0 Td 50.771605 Tz (All ) Tj 1.108333 0 Td 50.231481 Tz (readings ) Tj 2.586111 0 Td 58.333333 Tz (were ) Tj 1.575 0 Td 54.12037 Tz (normalized ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 40 0 0 40 0 771 Tm 8.175 0 Td 64.285714 Tz (vehicle ) Tj 3.225 0 Td 63.690476 Tz (control ) Tj 3.225 0 Td 59.166667 Tz (after ) Tj 2.275 0 Td 62.878788 Tz (subtraction ) Tj 4.725 0 Td 75 Tz (of ) Tj 1.35 0 Td 64.930556 Tz (fluorescence ) Tj 5.225 0 Td 60.416667 Tz (in ) Tj 1.3 0 Td 63.888889 Tz (the ) Tj 40 0 0 40 0 725 Tm 8.175 0 Td 70.833333 Tz (absence ) Tj 3.15 0 Td 70.833333 Tz (of ) Tj 0.95 0 Td 93.75 Tz (CCM. ) Tj 2.5 0 Td 71.875 Tz (Data ) Tj 1.85 0 Td 65.277778 Tz (are ) Tj 1.325 0 Td 80 Tz (shown ) Tj 2.55 0 Td 66.666667 Tz (as ) Tj 1 0 Td 62.5 Tz (the ) Tj 1.325 0 Td 76.388889 Tz (meantS.D. ) Tj 4.325 0 Td 67.708333 Tz (ofat ) Tj 1.8 0 Td 56.666667 Tz (least ) Tj 51.428571 0 0 51.428571 0 673.986667 Tm 6.338889 0 Td 49.259259 Tz (three ) Tj 1.652778 0 Td 46.450617 Tz (wells. ) Tj 1.847222 0 Td 50.771605 Tz (All ) Tj 1.069444 0 Td 53.619529 Tz (experiments ) Tj 3.733333 0 Td 59.143519 Tz (were ) Tj 1.594444 0 Td 51.041667 Tz (repeated ) Tj 2.586111 0 Td 46.990741 Tz (at ) Tj 0.738889 0 Td 44.074074 Tz (least ) Tj 1.477778 0 Td 52.5 Tz (twice ) Tj 1.711111 0 Td 61.574074 Tz (and ) Tj 40 0 0 40 0 634 Tm 8.175 0 Td 57.738095 Tz (results ) Tj 2.65 0 Td 65.277778 Tz (are ) Tj 1.425 0 Td 72.222222 Tz (shown. ) Tj 51.428571 0 0 51.428571 0 582.8 Tm 6.358333 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 49.421296 Tz (Kinetics ) Tj 2.547222 0 Td 56.712963 Tz (Assays ) Tj 51.428571 0 0 51.428571 0 538.095358 Tm 7.097222 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 46.990741 Tz (kinetics ) Tj 2.45 0 Td 51.311728 Tz (assays ) Tj 2.041667 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 56.17284 Tz (performed ) Tj 3.227778 0 Td 52.5 Tz (using ) Tj 1.730556 0 Td 49.259259 Tz (eight ) Tj 1.652778 0 Td 46.090535 Tz (different ) Tj 40 0 0 40 0 496 Tm 8.175 0 Td 64.880952 Tz (concentrations ) Tj 5.7 0 Td 72.916667 Tz (of ) Tj 1.025 0 Td 62.037037 Tz (Substrate ) Tj 3.575 0 Td 76.388889 Tz (and ) Tj 1.6 0 Td 76.388889 Tz (two ) Tj 1.675 0 Td 59.259259 Tz (different ) Tj 3.45 0 Td 64.583333 Tz (concentrations ) Tj 51.428571 0 0 51.428571 0 446.004831 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 46.8107 Tz (inhibitor ) Tj 2.663889 0 Td 57.523148 Tz (\(ChemBridge, ) Tj 4.336111 0 Td 58.333333 Tz (San ) Tj 1.263889 0 Td 52.932099 Tz (Diego, ) Tj 2.080556 0 Td 42.534722 Tz (Calif.\). ) Tj 2.216667 0 Td 63.734568 Tz (The ) Tj 1.322222 0 Td 56.712963 Tz (FS-3 ) Tj 1.575 0 Td 68.055556 Tz (sub ) Tj 51.428571 0 0 51.428571 0 398.854033 Tm 6.377778 0 Td 43.75 Tz (strate ) Tj 1.711111 0 Td 50.694444 Tz (concentrations ) Tj 4.491667 0 Td 54.012346 Tz (ranged ) Tj 2.119444 0 Td 58.333333 Tz (from ) Tj 1.594444 0 Td 51.311728 Tz (20-0.3 ) Tj 2.1 0 Td 81.018519 Tz (uM ) Tj 1.166667 0 Td 58.333333 Tz (on ) Tj 0.894444 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 43.75 Tz (plate. ) Tj 51.428571 0 0 51.428571 0 352.030675 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.244444 0 Td 54.444444 Tz (normalized ) Tj 3.402778 0 Td 50.231481 Tz (fluorescence ) Tj 3.733333 0 Td 44.907407 Tz (results ) Tj 2.002778 0 Td 59.953704 Tz (were ) Tj 1.516667 0 Td 48.611111 Tz (plotted ) Tj 2.138889 0 Td 50.231481 Tz (as ) Tj 0.719444 0 Td 55.092593 Tz (a ) Tj 0.427778 0 Td 64.00463 Tz (func ) Tj 40 0 0 40 0 313 Tm 8.15 0 Td 61.458333 Tz (tion ) Tj 1.675 0 Td 70.833333 Tz (of ) Tj 0.95 0 Td 68.75 Tz (time ) Tj 1.825 0 Td 56.25 Tz (in ) Tj 0.9 0 Td 65.833333 Tz (order ) Tj 2.075 0 Td 62.5 Tz (to ) Tj 0.925 0 Td 69.444444 Tz (determine ) Tj 3.9 0 Td 51.785714 Tz (initial ) Tj 2.375 0 Td 54.166667 Tz (rates. ) Tj 2.125 0 Td 81.944444 Tz (The ) Tj 1.65 0 Td 51.190476 Tz (initial ) Tj 2.35 0 Td 57.5 Tz (rates ) Tj 51.428571 0 0 51.428571 0 262.007101 Tm 6.338889 0 Td 59.953704 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (plotted ) Tj 2.177778 0 Td 49.537037 Tz (against ) Tj 2.197222 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 47.890947 Tz (Substrate ) Tj 2.722222 0 Td 50.605413 Tz (concentration ) Tj 4.083333 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 55.092593 Tz (a ) Tj 0.447222 0 Td 56.17284 Tz (rectan ) Tj 51.428571 0 0 51.428571 0 217.535912 Tm 6.358333 0 Td 51.203704 Tz (gular ) Tj 1.886111 0 Td 51.527778 Tz (hyperbolic ) Tj 3.5 0 Td 53.796296 Tz (curve ) Tj 2.002778 0 Td 61.574074 Tz (was ) Tj 1.497222 0 Td 42.12963 Tz (fitted ) Tj 1.866667 0 Td 48.611111 Tz (to ) Tj 0.952778 0 Td 50.771605 Tz (the ) Tj 1.302778 0 Td 51.041667 Tz (data ) Tj 1.594444 0 Td 53.148148 Tz (using ) Tj 1.983333 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 172.763819 Tm 6.377778 0 Td 56.17284 Tz (KaleidaGraph ) Tj 4.433333 0 Td 51.851852 Tz (software ) Tj 2.819444 0 Td 55.092593 Tz (\(Synergy ) Tj 3.033333 0 Td 50.771605 Tz (Software, ) Tj 3.188889 0 Td 52.662037 Tz (Reading, ) Tj 2.916667 0 Td 42.939815 Tz (Pa., ) Tj 30 0 0 30 0 2547 Tm 41.666667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 2339 Tm 41.666667 0 Td 72.222222 Tz (15 ) Tj 30 0 0 30 0 1923 Tm 41.6 0 Td 77.777778 Tz (25 ) Tj 30 0 0 30 0 1716 Tm 41.6 0 Td 80.555556 Tz (30 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 30 0 0 30 0 1299 Tm 41.566667 0 Td 83.333333 Tz (40 ) Tj 30 0 0 30 0 1091 Tm 41.566667 0 Td 80.555556 Tz (45 ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 30 0 0 30 0 467 Tm 41.633333 0 Td 77.777778 Tz (60 ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.881081 0 Td 72.522523 Tz (8 ) Tj 51.428571 0 0 51.428571 0 2913 Tm 25.297222 0 Td 52.777778 Tz (Version ) Tj 2.488889 0 Td 46.450617 Tz (4.03\). ) Tj 1.944444 0 Td 62.654321 Tz (The ) Tj 1.419444 0 Td 84.259259 Tz (K ) Tj 1.166667 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 51.851852 Tz (V, ) Tj 1.730556 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 49.259259 Tz (calculated ) Tj 3.247222 0 Td 57.523148 Tz (from ) Tj 1.652778 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 2867.055758 Tm 25.297222 0 Td 47.170782 Tz (resulting ) Tj 2.722222 0 Td 43.75 Tz (plots. ) Tj 1.788889 0 Td 71.296296 Tz (Mode ) Tj 1.886111 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 46.990741 Tz (inhibition ) Tj 3.013889 0 Td 60.493827 Tz (was ) Tj 1.302778 0 Td 54.444444 Tz (determined ) Tj 3.461111 0 Td 59.143519 Tz (from ) Tj 1.594444 0 Td 50.771605 Tz (the ) Tj 52.857143 0 0 52.857143 0 2817 Tm 24.613514 0 Td 45.545546 Tz (inhibitor ) Tj 2.554054 0 Td 45.195195 Tz (effect ) Tj 1.778378 0 Td 55.18018 Tz (on ) Tj 0.832432 0 Td 74.099099 Tz (K, ) Tj 1.040541 0 Td 56.756757 Tz (and ) Tj 1.135135 0 Td 81.981982 Tz (V ) Tj 1.57027 0 Td 45.495495 Tz (values. ) Tj 2.062162 0 Td 62.012012 Tz (The ) Tj 1.267568 0 Td 46.509009 Tz (dissociation ) Tj 3.518919 0 Td 68.318318 Tz (con ) Tj 52.857143 0 0 52.857143 0 2770.135922 Tm 24.632432 0 Td 43.513514 Tz (stant ) Tj 1.494595 0 Td 62.012012 Tz (\(K\) ) Tj 1.286486 0 Td 46.246246 Tz (for ) Tj 0.983784 0 Td 44.844845 Tz (inhibitor ) Tj 2.554054 0 Td 52.702703 Tz (binding ) Tj 2.345946 0 Td 60.960961 Tz (was ) Tj 1.248649 0 Td 48.243243 Tz (calculated ) Tj 3.008108 0 Td 48.348348 Tz (for ) Tj 0.983784 0 Td 53.603604 Tz (each ) Tj 1.456757 0 Td 55.18018 Tz (of ) Tj 0.737838 0 Td 49.399399 Tz (the ) Tj 51.428571 0 0 51.428571 0 2724.135338 Tm 25.297222 0 Td 44.781145 Tz (inhibitors. ) Tj 3.305556 0 Td 53.472222 Tz (K, ) Tj 1.011111 0 Td 47.530864 Tz (for ) Tj 1.147222 0 Td 53.098291 Tz (uncompetitive ) Tj 4.452778 0 Td 46.990741 Tz (inhibition ) Tj 3.15 0 Td 62.654321 Tz (was ) Tj 1.438889 0 Td 49.583333 Tz (calculated ) Tj 51.428571 0 0 51.428571 0 2678.564295 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.808333 0 Td 53.472222 Tz (Equation ) Tj 2.8 0 Td 32.407407 Tz (1 ) Tj 0.447222 0 Td 59.41358 Tz (\(Cheng ) Tj 2.294444 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 46.585648 Tz (Prusoff, ) Tj 2.508333 0 Td 49.151235 Tz (1973\). ) Tj 1.983333 0 Td 53.877315 Tz (Equation ) Tj 2.780556 0 Td 55.092593 Tz (2 ) Tj 0.505556 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 2628.835821 Tm 25.277778 0 Td 55.902778 Tz (used ) Tj 1.613889 0 Td 46.450617 Tz (for ) Tj 1.05 0 Td 51.851852 Tz (competitive ) Tj 3.655556 0 Td 46.990741 Tz (inhibition ) Tj 3.091667 0 Td 58.873457 Tz (\(Cheng ) Tj 2.352778 0 Td 59.41358 Tz (and ) Tj 1.322222 0 Td 46.990741 Tz (Prusoff, ) Tj 2.605556 0 Td 49.151235 Tz (1973\). ) Tj 52.857143 0 0 52.857143 0 2579.155556 Tm 24.613514 0 Td 62.012012 Tz (The ) Tj 1.210811 0 Td 52.702703 Tz (average ) Tj 2.364865 0 Td 46.246246 Tz (substrate ) Tj 2.62973 0 Td 85.135135 Tz (K ) Tj 1.078378 0 Td 45.945946 Tz (values, ) Tj 2.081081 0 Td 51.501502 Tz (3.7+/- ) Tj 1.92973 0 Td 44.144144 Tz (1.9 ) Tj 1.002703 0 Td 77.252252 Tz (uM ) Tj 1.078378 0 Td 50 Tz (\(n=22\), ) Tj 2.232432 0 Td 57.545045 Tz (were ) Tj 52.857143 0 0 52.857143 0 2531.622166 Tm 24.613514 0 Td 47.927928 Tz (calculated ) Tj 3.102703 0 Td 51.081081 Tz (using ) Tj 1.721622 0 Td 48.348348 Tz (the ) Tj 1.078378 0 Td 47.297297 Tz (individual ) Tj 3.083784 0 Td 78.828829 Tz (K ) Tj 1.097297 0 Td 48.873874 Tz (values ) Tj 2.005405 0 Td 52.657658 Tz (determined ) Tj 3.386486 0 Td 50.45045 Tz (using ) Tj 51.428571 0 0 51.428571 0 2488.742621 Tm 25.297222 0 Td 50.084175 Tz (rectangular ) Tj 3.402778 0 Td 51.527778 Tz (hyperbolic ) Tj 3.247222 0 Td 53.796296 Tz (curve ) Tj 1.769444 0 Td 40.740741 Tz (fitting ) Tj 1.827778 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 46.666667 Tz (plots ) Tj 1.555556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 39.814815 Tz (initial ) Tj 1.827778 0 Td 48.206019 Tz (velocity ) Tj 51.428571 0 0 51.428571 0 2436.205219 Tm 25.297222 0 Td 50.771605 Tz (Versus ) Tj 2.002778 0 Td 47.530864 Tz (Substrate ) Tj 2.741667 0 Td 50.356125 Tz (concentration ) Tj 4.083333 0 Td 58.333333 Tz (from ) Tj 1.575 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 39.969136 Tz (all ) Tj 0.875 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 51.446759 Tz (analyses ) Tj 51.428571 0 0 51.428571 0 2387 Tm 25.297222 0 Td 49.691358 Tz (for ) Tj 1.088889 0 Td 51.851852 Tz (FS-3. ) Tj 1.827778 0 Td 55.092593 Tz (For ) Tj 1.225 0 Td 58.981481 Tz (mixed ) Tj 2.002778 0 Td 67.24537 Tz (mode ) Tj 1.827778 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 75.833333 Tz (KICso ) Tj 2.605556 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 60.185185 Tz (assumed ) Tj 51.428571 0 0 51.428571 0 2342.036145 Tm 25.316667 0 Td 55.681818 Tz (\(Burlingham ) Tj 3.869444 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 51.851852 Tz (Widlanski, ) Tj 3.325 0 Td 50.771605 Tz (2003\). ) Tj 51.428571 0 0 51.428571 0 2281.684783 Tm 26.036111 0 Td 57.175926 Tz (Pharmacophores ) Tj 5.152778 0 Td 53.472222 Tz (4a-d ) Tj 1.594444 0 Td 59.143519 Tz (were ) Tj 1.711111 0 Td 51.041667 Tz (able ) Tj 1.555556 0 Td 43.75 Tz (to ) Tj 0.836111 0 Td 52.777778 Tz (achieve ) Tj 2.508333 0 Td 43.209877 Tz (hit ) Tj 1.108333 0 Td 44.722222 Tz (rates ) Tj 1.633333 0 Td 59.953704 Tz (of ) Tj 51.428571 0 0 51.428571 0 2234.618375 Tm 25.297222 0 Td 56.712963 Tz (28.6%, ) Tj 2.275 0 Td 54.552469 Tz (18.5%, ) Tj 2.119444 0 Td 63.518519 Tz (21.1% ) Tj 2.002778 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 56.712963 Tz (32.3%, ) Tj 2.216667 0 Td 46.118234 Tz (respectively. ) Tj 3.752778 0 Td 64.490741 Tz (Pharmacoph ) Tj 48.571429 0 0 48.571429 0 2186 Tm 26.785294 0 Td 53.186275 Tz (ores ) Tj 1.420588 0 Td 56.617647 Tz (5a-d ) Tj 1.482353 0 Td 62.622549 Tz (were ) Tj 1.626471 0 Td 53.186275 Tz (able ) Tj 1.4 0 Td 48.039216 Tz (to ) Tj 0.720588 0 Td 55.392157 Tz (achieve ) Tj 2.429412 0 Td 46.895425 Tz (hit ) Tj 0.967647 0 Td 48.039216 Tz (rates ) Tj 1.585294 0 Td 56.617647 Tz (of ) Tj 0.741176 0 Td 67.48366 Tz (0%, ) Tj 1.358824 0 Td 60.04902 Tz (25.8%, ) Tj 2.326471 0 Td 66.339869 Tz (0%, ) Tj 1.297059 0 Td 64.052288 Tz (and ) Tj 51.428571 0 0 51.428571 0 2140.282528 Tm 25.297222 0 Td 57.253086 Tz (35.0%, ) Tj 2.313889 0 Td 45.868946 Tz (respectively. ) Tj 3.888889 0 Td 57.407407 Tz (Pharmacophores ) Tj 5.075 0 Td 59.953704 Tz (4d ) Tj 0.952778 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 58.333333 Tz (5d ) Tj 0.933333 0 Td 56.712963 Tz (have ) Tj 1.594444 0 Td 58.333333 Tz (been ) Tj 51.428571 0 0 51.428571 0 2091.693034 Tm 25.297222 0 Td 51.041667 Tz (able ) Tj 1.341667 0 Td 46.990741 Tz (identify ) Tj 2.411111 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 45.833333 Tz (largest ) Tj 2.041667 0 Td 51.851852 Tz (percentages ) Tj 3.558333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 47.530864 Tz (active ) Tj 1.808333 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 44.781145 Tz (inhibitors. ) Tj 51.428571 0 0 51.428571 0 2045.607282 Tm 25.316667 0 Td 58.333333 Tz (Pharmacophore ) Tj 4.841667 0 Td 59.953704 Tz (4b ) Tj 1.069444 0 Td 60.493827 Tz (was ) Tj 1.4 0 Td 51.041667 Tz (able ) Tj 1.516667 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 46.585648 Tz (identify ) Tj 2.547222 0 Td 49.691358 Tz (the ) Tj 1.186111 0 Td 51.311728 Tz (highly ) Tj 2.158333 0 Td 51.311728 Tz (potent ) Tj 51.428571 0 0 51.428571 0 1993.758355 Tm 25.297222 0 Td 61.574074 Tz (compounds ) Tj 3.577778 0 Td 78.858025 Tz (NSC ) Tj 1.652778 0 Td 60.763889 Tz (5014 ) Tj 1.672222 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 77.777778 Tz (NSC ) Tj 1.672222 0 Td 58.981481 Tz (12859 ) Tj 1.983333 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 59.953704 Tz (5b ) Tj 0.933333 0 Td 63.734568 Tz (was ) Tj 1.380556 0 Td 51.041667 Tz (able ) Tj 1.438889 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 1945.216252 Tm 25.297222 0 Td 46.990741 Tz (identify ) Tj 2.527778 0 Td 76.697531 Tz (NSC ) Tj 1.652778 0 Td 55.632716 Tz (75779. ) Tj 2.294444 0 Td 76.697531 Tz (NSC ) Tj 1.652778 0 Td 56.018519 Tz (341348, ) Tj 2.586111 0 Td 59.62963 Tz (which ) Tj 2.061111 0 Td 51.851852 Tz (has ) Tj 1.205556 0 Td 59.41358 Tz (and ) Tj 1.361111 0 Td 54.012346 Tz (ICs ) Tj 1.516667 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1899.440191 Tm 25.297222 0 Td 53.472222 Tz (2.50 ) Tj 1.438889 0 Td 62.654321 Tz (uM, ) Tj 1.283333 0 Td 60.493827 Tz (was ) Tj 1.205556 0 Td 46.018519 Tz (identified ) Tj 2.897222 0 Td 56.712963 Tz (from ) Tj 1.497222 0 Td 59.41358 Tz (two ) Tj 1.205556 0 Td 55.092593 Tz (pharmacophores, ) Tj 5.094444 0 Td 56.712963 Tz (4a ) Tj 0.816667 0 Td 58.333333 Tz (and ) Tj 1.127778 0 Td 48.611111 Tz (4c. ) Tj 51.428571 0 0 51.428571 0 1849 Tm 25.277778 0 Td 79.938272 Tz (NSC ) Tj 1.691667 0 Td 54.552469 Tz (77520, ) Tj 2.216667 0 Td 58.333333 Tz (which ) Tj 2.002778 0 Td 54.012346 Tz (has ) Tj 1.225 0 Td 56.712963 Tz (an ) Tj 0.952778 0 Td 52.932099 Tz (ICs ) Tj 1.497222 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 53.472222 Tz (4.07 ) Tj 1.555556 0 Td 62.654321 Tz (uM, ) Tj 1.4 0 Td 61.574074 Tz (was ) Tj 1.380556 0 Td 45.694444 Tz (identified ) Tj 51.428571 0 0 51.428571 0 1804.813836 Tm 25.297222 0 Td 58.333333 Tz (from ) Tj 1.672222 0 Td 58.333333 Tz (pharmacophore ) Tj 4.841667 0 Td 48.611111 Tz (4d. ) Tj 1.166667 0 Td 63.734568 Tz (The ) Tj 1.419444 0 Td 52.211934 Tz (following ) Tj 3.111111 0 Td 46.450617 Tz (tables ) Tj 1.963889 0 Td 61.574074 Tz (show ) Tj 1.788889 0 Td 50.555556 Tz (these ) Tj 40 0 0 40 0 1761 Tm 32.525 0 Td 55.208333 Tz (results: ) Tj 38.571429 0 0 38.571429 0 1670 Tm 43.477778 0 Td 101.975309 Tz (TABLE ) Tj 3.266667 0 Td 77.777778 Tz (3 ) Tj 40 0 0 40 0 1594.092308 Tm 38.525 0 Td 51.515152 Tz (Preliminary ) Tj 3.6 0 Td 51.388889 Tz (screen ) Tj 2.05 0 Td 56.25 Tz (of ) Tj 0.825 0 Td 58.333333 Tz (102 ) Tj 1.225 0 Td 46.25 Tz (identified ) Tj 40 0 0 40 0 1557.099217 Tm 38.575 0 Td 62.037037 Tz (compounds ) Tj 3.55 0 Td 57.291667 Tz (from ) Tj 1.575 0 Td 50 Tz (the ) Tj 1.075 0 Td 45.833333 Tz (virtual ) Tj 2.075 0 Td 48.214286 Tz (screen. ) Tj 34.285714 0 0 34.285714 0 1485.29064 Tm 44.479167 0 Td 89.12037 Tz (NSC ) Tj 1.808333 0 Td 34.027778 Tz (if ) Tj 7.408333 0 Td 116.666667 Tz (% ) Tj 0.9625 0 Td 66.840278 Tz (Response ) Tj 30 0 0 30 0 1416 Tm 51.1 0 Td 81.111111 Tz (45622 ) Tj 11.1 0 Td 102.222222 Tz (163.1 ) Tj 30 0 0 30 0 1379 Tm 51.166667 0 Td 80 Tz (65574 ) Tj 10.966667 0 Td 106.666667 Tz (2O3.7 ) Tj 30 0 0 30 0 1341 Tm 51.133333 0 Td 80 Tz (75779 ) Tj 11 0 Td 106.666667 Tz (205.7 ) Tj 30 0 0 30 0 1304 Tm 50.633333 0 Td 80.555556 Tz (338310 ) Tj 11.5 0 Td 106.666667 Tz (242.9 ) Tj 30 0 0 30 0 1267 Tm 51.2 0 Td 77.777778 Tz (12859 ) Tj 10.933333 0 Td 80.555556 Tz (27 ) Tj 2 0 Td 66.666667 Tz (2.8 ) Tj 30 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Tj 11.633333 0 Td 75.925926 Tz (805 ) Tj 2 0 Td 102.777778 Tz (nM ) Tj 35.714286 0 0 35.714286 0 2681.979592 Tm 43.344 0 Td 68.133333 Tz (75779 ) Tj 9.632 0 Td 57.166667 Tz (1.26 ) Tj 2.212 0 Td 116.666667 Tz (M ) Tj 35.714286 0 0 35.714286 0 2648.622222 Tm 43.764 0 Td 68.833333 Tz (SO14 ) Tj 9.212 0 Td 57.166667 Tz (1.27 ) Tj 2.156 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2614.163636 Tm 42.952 0 Td 67.666667 Tz (341348 ) Tj 9.968 0 Td 59.5 Tz (2.50 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2577.789809 Tm 43.344 0 Td 68.133333 Tz (77520 ) Tj 9.548 0 Td 60.666667 Tz (4.07 ) Tj 2.1 0 Td 74.666667 Tz (iM ) Tj 35.714286 0 0 35.714286 0 2542.85906 Tm 43.372 0 Td 66.266667 Tz (80903 ) Tj 9.548 0 Td 59.5 Tz (5.88 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2507.899329 Tm 43.344 0 Td 56 Tz (795.93 ) Tj 9.604 0 Td 58.333333 Tz (6.36 ) Tj 2.184 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2471.583942 Tm 43.764 0 Td 68.833333 Tz (7234 ) Tj 9.156 0 Td 59.5 Tz (7.02 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2436.881579 Tm 43.344 0 Td 68.133333 Tz (79742 ) Tj 9.576 0 Td 60.666667 Tz (7.04 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2402.163636 Tm 42.952 0 Td 58 Tz (33.8310 ) Tj 9.968 0 Td 59.5 Tz (7.96 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2365.918919 Tm 43.344 0 Td 67.2 Tz (79743 ) Tj 9.604 0 Td 57.166667 Tz (8.33 ) Tj 2.184 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2330.96 Tm 43.316 0 Td 69.066667 Tz (4562O ) Tj 9.632 0 Td 57.166667 Tz (8.85 ) Tj 2.184 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2295.837838 Tm 43.372 0 Td 65.333333 Tz (65851 ) Tj 9.548 0 Td 59.5 Tz (9.50 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2259.85906 Tm 43.4 0 Td 66.266667 Tz (11246 ) Tj 9.52 0 Td 59.5 Tz (0.20 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2224.96 Tm 43.344 0 Td 69.066667 Tz (79744 ) Tj 9.632 0 Td 57.166667 Tz (1.52 ) Tj 2.156 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2190.062069 Tm 43.316 0 Td 69.066667 Tz (45622 ) Tj 9.66 0 Td 53.666667 Tz (1.61 ) Tj 2.212 0 Td 116.666667 Tz (M ) Tj 35.714286 0 0 35.714286 0 2153.959459 Tm 43.344 0 Td 56.777778 Tz (58.057 ) Tj 9.632 0 Td 56 Tz (1.63 ) Tj 2.156 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2118.939597 Tm 43.372 0 Td 68.133333 Tz (65574 ) Tj 9.548 0 Td 59.5 Tz (2.02 ) Tj 2.268 0 Td 116.666667 Tz (M ) Tj 35.714286 0 0 35.714286 0 2083.837838 Tm 43.4 0 Td 65.333333 Tz (11243 ) Tj 9.52 0 Td 59.5 Tz (2.57 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2047.552239 Tm 43.764 0 Td 66.5 Tz (7815 ) Tj 9.156 0 Td 58.333333 Tz (3.43 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 2012.881579 Tm 43.344 0 Td 68.133333 Tz (58058 ) Tj 9.576 0 Td 60.666667 Tz (3.84 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1977.88 Tm 43.316 0 Td 67.2 Tz (43891 ) Tj 9.604 0 Td 59.5 Tz (3.92 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1941.88 Tm 43.372 0 Td 67.2 Tz (6S848 ) Tj 9.548 0 Td 59.5 Tz (5.19 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1906.918919 Tm 43.372 0 Td 67.2 Tz (65576 ) Tj 9.548 0 Td 57.166667 Tz (5.51 ) Tj 2.212 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1871.878378 Tm 43.372 0 Td 66.266667 Tz (65855 ) Tj 9.548 0 Td 60.666667 Tz (7.44 ) Tj 2.268 0 Td 116.666667 Tz (M ) Tj 35.714286 0 0 35.714286 0 1835.980132 Tm 43.316 0 Td 70 Tz (47764 ) Tj 9.632 0 Td 57.166667 Tz (8.23 ) Tj 2.184 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1800.878378 Tm 43.372 0 Td 66.266667 Tz (65575 ) Tj 9.576 0 Td 58.333333 Tz (8.56 ) Tj 2.184 0 Td 126 Tz (M ) Tj 35.714286 0 0 35.714286 0 1765.766234 Tm 43.372 0 Td 66.266667 Tz (65573 ) Tj 9.548 0 Td 59.5 Tz (9.08 ) Tj 2.072 0 Td 74.666667 Tz (IM ) Tj 35.714286 0 0 35.714286 0 1729.650307 Tm 43.372 0 Td 67.2 Tz (65869 ) Tj 9.156 0 Td 60.666667 Tz (22.67 ) Tj 2.632 0 Td 121.333333 Tz (M ) Tj 35.714286 0 0 35.714286 0 1694.703704 Tm 43.316 0 Td 68.133333 Tz (47755 ) Tj 9.212 0 Td 58.8 Tz (37.61 ) Tj 2.632 0 Td 121.333333 Tz (M ) Tj 40 0 0 40 0 1579 Tm 33.45 0 Td 81.944444 Tz (The ) Tj 1.7 0 Td 66.025641 Tz (determination ) Tj 5.375 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 65 Tz (these ) Tj 2.175 0 Td 62.5 Tz (inventive ) Tj 3.5 0 Td 101.388889 Tz (ATX ) Tj 2.05 0 Td 60 Tz (inhibition ) Tj 3.825 0 Td 106.944444 Tz (com ) Tj 51.428571 0 0 51.428571 0 1519.306892 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.469444 0 Td 61.574074 Tz (was ) Tj 1.438889 0 Td 51.041667 Tz (thus ) Tj 1.575 0 Td 55.740741 Tz (based ) Tj 2.022222 0 Td 59.953704 Tz (upon ) Tj 1.788889 0 Td 58.333333 Tz (a ) Tj 0.738889 0 Td 53.06713 Tz (modified ) Tj 2.897222 0 Td 58.084046 Tz (pharmacophore ) Tj 51.428571 0 0 51.428571 0 1464.107399 Tm 25.297222 0 Td 60.277778 Tz (model ) Tj 1.963889 0 Td 50.87963 Tz (generation ) Tj 3.208333 0 Td 46.180556 Tz (that ) Tj 1.244444 0 Td 53.877315 Tz (provided ) Tj 2.722222 0 Td 58.333333 Tz (a ) Tj 0.466667 0 Td 51.851852 Tz (highly ) Tj 2.041667 0 Td 48.287037 Tz (Surprising ) Tj 3.013889 0 Td 74.537037 Tz (30% ) Tj 1.516667 0 Td 71.296296 Tz (con ) Tj 40 0 0 40 0 1411 Tm 32.525 0 Td 64.285714 Tz (fidence ) Tj 3.075 0 Td 57.291667 Tz (rate ) Tj 1.725 0 Td 58.333333 Tz (in ) Tj 1.075 0 Td 69.166667 Tz (terms ) Tj 2.425 0 Td 75 Tz (of ) Tj 1.1 0 Td 100 Tz (ATX ) Tj 2.175 0 Td 60 Tz (inhibition ) Tj 4 0 Td 70.512821 Tz (measurements. ) Tj 5.85 0 Td 85.416667 Tz (As ) Tj 51.428571 0 0 51.428571 0 1349.97171 Tm 25.316667 0 Td 49.907407 Tz (Such, ) Tj 1.711111 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 44.444444 Tz (ability ) Tj 2.080556 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 48.611111 Tz (predict ) Tj 2.216667 0 Td 54.552469 Tz (proper ) Tj 2.138889 0 Td 49.691358 Tz (autotaxin ) Tj 2.936111 0 Td 46.666667 Tz (inhibition ) Tj 3.013889 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1294.52801 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.255556 0 Td 38.888889 Tz (is ) Tj 0.602778 0 Td 53.652263 Tz (extremely ) Tj 3.052778 0 Td 40.833333 Tz (difficult; ) Tj 2.605556 0 Td 54.282407 Tz (however, ) Tj 2.780556 0 Td 52.777778 Tz (through ) Tj 2.391667 0 Td 42.939815 Tz (this ) Tj 1.225 0 Td 53.472222 Tz (modified ) Tj 51.428571 0 0 51.428571 0 1241.204465 Tm 25.297222 0 Td 58.084046 Tz (pharmacophore ) Tj 4.686111 0 Td 57.118056 Tz (modeling ) Tj 2.897222 0 Td 55.555556 Tz (method, ) Tj 2.488889 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 45.046296 Tz (relatively ) Tj 2.858333 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 59.548611 Tz (unexpect ) Tj 51.428571 0 0 51.428571 0 1185.647059 Tm 25.297222 0 Td 51.851852 Tz (edly ) Tj 1.438889 0 Td 53.472222 Tz (high ) Tj 1.497222 0 Td 53.472222 Tz (acceptance ) Tj 3.422222 0 Td 44.560185 Tz (rate ) Tj 1.244444 0 Td 52.662037 Tz (provides ) Tj 2.722222 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 48.070988 Tz (Surprisingly ) Tj 3.655556 0 Td 60.763889 Tz (good ) Tj 1.652778 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1125.175879 Tm 25.297222 0 Td 50 Tz (fidence ) Tj 2.313889 0 Td 46.180556 Tz (rate ) Tj 1.322222 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 50.925926 Tz (derived ) Tj 2.372222 0 Td 61.574074 Tz (compounds ) Tj 3.538889 0 Td 52.211934 Tz (generated ) Tj 3.072222 0 Td 46.990741 Tz (in ) Tj 0.797222 0 Td 54.282407 Tz (Such ) Tj 1.536111 0 Td 55.092593 Tz (a ) Tj 48.571429 0 0 48.571429 0 1068 Tm 26.826471 0 Td 56.862745 Tz (manner. ) Tj 2.861765 0 Td 49.754902 Tz (In ) Tj 1.029412 0 Td 53.186275 Tz (essence, ) Tj 2.985294 0 Td 45.465686 Tz (this ) Tj 1.544118 0 Td 54.638009 Tz (determination ) Tj 4.694118 0 Td 61.764706 Tz (of ) Tj 1.070588 0 Td 49.754902 Tz (suitable ) Tj 2.779412 0 Td 82.352941 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1012.649746 Tm 25.297222 0 Td 46.018519 Tz (inhibitors ) Tj 3.052778 0 Td 53.240741 Tz (through ) Tj 2.508333 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 59.953704 Tz (method ) Tj 2.430556 0 Td 45.37037 Tz (that ) Tj 1.322222 0 Td 52.572016 Tz (generated ) Tj 3.111111 0 Td 54.444444 Tz (fewer ) Tj 1.886111 0 Td 50.231481 Tz (than ) Tj 1.477778 0 Td 60.493827 Tz (300 ) Tj 51.428571 0 0 51.428571 0 956.621359 Tm 25.297222 0 Td 40.277778 Tz (initial ) Tj 1.847222 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 45.37037 Tz (testing ) Tj 2.080556 0 Td 58.333333 Tz (from ) Tj 1.575 0 Td 56.712963 Tz (an ) Tj 0.855556 0 Td 39.814815 Tz (initial ) Tj 1.847222 0 Td 52.256944 Tz (database ) Tj 2.663889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 51.851852 Tz (250, ) Tj 51.428571 0 0 51.428571 0 900.029268 Tm 25.297222 0 Td 61.574074 Tz (000 ) Tj 1.283333 0 Td 45.37037 Tz (structures, ) Tj 3.169444 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 48.935185 Tz (ultimately ) Tj 3.15 0 Td 47.800926 Tz (resulted ) Tj 2.469444 0 Td 46.990741 Tz (in ) Tj 0.680556 0 Td 46.180556 Tz (just ) Tj 1.263889 0 Td 55.092593 Tz (over ) Tj 1.536111 0 Td 58.333333 Tz (100 ) Tj 1.166667 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 846.052443 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.255556 0 Td 47.530864 Tz (for ) Tj 0.972222 0 Td 42.12963 Tz (final ) Tj 1.419444 0 Td 48.611111 Tz (analysis ) Tj 2.469444 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 75.617284 Tz (ATX ) Tj 1.536111 0 Td 46.666667 Tz (inhibition ) Tj 2.955556 0 Td 61.574074 Tz (was ) Tj 1.263889 0 Td 53.472222 Tz (unexpectedly ) Tj 51.428571 0 0 51.428571 0 788.887755 Tm 25.297222 0 Td 59.953704 Tz (good ) Tj 1.672222 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 58.981481 Tz (shows ) Tj 1.983333 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 46.8107 Tz (potential ) Tj 2.780556 0 Td 50.555556 Tz (value ) Tj 1.769444 0 Td 47.530864 Tz (for ) Tj 1.069444 0 Td 53.472222 Tz (Such ) Tj 1.516667 0 Td 51.203704 Tz (types ) Tj 1.75 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 55.092593 Tz (deter ) Tj 51.428571 0 0 51.428571 0 732.212548 Tm 25.297222 0 Td 52.932099 Tz (minations ) Tj 3.227778 0 Td 53.240741 Tz (through ) Tj 2.605556 0 Td 49.691358 Tz (the ) Tj 1.225 0 Td 54.372428 Tz (avoidance ) Tj 3.286111 0 Td 58.333333 Tz (of ) Tj 0.952778 0 Td 46.759259 Tz (testing ) Tj 2.275 0 Td 54.012346 Tz (thousands ) Tj 3.305556 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 677.86747 Tm 25.297222 0 Td 47.170782 Tz (potential ) Tj 2.761111 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 53.240741 Tz (through ) Tj 2.469444 0 Td 56.388889 Tz (rough ) Tj 1.886111 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 46.990741 Tz (inhibition ) Tj 3.052778 0 Td 58.333333 Tz (screen ) Tj 51.428571 0 0 51.428571 0 621.773869 Tm 25.297222 0 Td 45.37037 Tz (ings. ) Tj 1.691667 0 Td 63.734568 Tz (The ) Tj 1.438889 0 Td 58.333333 Tz (pharmacophore ) Tj 4.880556 0 Td 55.092593 Tz (model, ) Tj 2.313889 0 Td 46.180556 Tz (particularly ) Tj 3.694444 0 Td 43.75 Tz (in ) Tj 0.875 0 Td 53.877315 Tz (modified ) Tj 51.428571 0 0 51.428571 0 562.138298 Tm 25.297222 0 Td 58.333333 Tz (form ) Tj 1.730556 0 Td 45.37037 Tz (to ) Tj 0.875 0 Td 49.421296 Tz (increase ) Tj 2.702778 0 Td 49.691358 Tz (the ) Tj 1.244444 0 Td 43.013468 Tz (restrictive ) Tj 3.188889 0 Td 43.75 Tz (result ) Tj 1.886111 0 Td 46.990741 Tz (if ) Tj 0.758333 0 Td 58.333333 Tz (an ) Tj 1.011111 0 Td 45.910494 Tz (entire ) Tj 2.002778 0 Td 49.537037 Tz (6-point ) Tj 51.428571 0 0 51.428571 0 509.256348 Tm 25.297222 0 Td 50.771605 Tz (parent ) Tj 1.963889 0 Td 58.333333 Tz (pharmacophore ) Tj 4.725 0 Td 38.888889 Tz (is ) Tj 0.680556 0 Td 50.05144 Tz (followed, ) Tj 2.897222 0 Td 50.231481 Tz (thus ) Tj 1.380556 0 Td 51.851852 Tz (permits ) Tj 2.352778 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 59.41358 Tz (method ) Tj 2.333333 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 453.45283 Tm 25.297222 0 Td 52.211934 Tz (providing ) Tj 2.975 0 Td 46.990741 Tz (Suitable ) Tj 2.391667 0 Td 44.907407 Tz (results ) Tj 2.041667 0 Td 46.450617 Tz (for ) Tj 0.933333 0 Td 78.858025 Tz (ATX ) Tj 1.555556 0 Td 47.638889 Tz (inhibiting ) Tj 2.975 0 Td 58.333333 Tz (compounds, ) Tj 3.694444 0 Td 50.771605 Tz (not ) Tj 51.428571 0 0 51.428571 0 397.796209 Tm 25.277778 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 56.018519 Tz (mention ) Tj 2.488889 0 Td 47.138047 Tz (potentially ) Tj 3.227778 0 Td 58.333333 Tz (any ) Tj 1.225 0 Td 49.907407 Tz (other ) Tj 1.613889 0 Td 51.851852 Tz (type ) Tj 1.380556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 52.777778 Tz (pharmaceutical ) Tj 4.569444 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 338.05974 Tm 25.297222 0 Td 55.092593 Tz (pound, ) Tj 2.313889 0 Td 53.240741 Tz (without ) Tj 2.527778 0 Td 50.771605 Tz (the ) Tj 1.263889 0 Td 55.902778 Tz (need ) Tj 1.633333 0 Td 46.990741 Tz (to ) Tj 0.894444 0 Td 47.530864 Tz (invest ) Tj 2.022222 0 Td 53.20216 Tz (unreasonable ) Tj 4.141667 0 Td 54.282407 Tz (time ) Tj 1.594444 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 282.67044 Tm 25.297222 0 Td 50.771605 Tz (resources ) Tj 3.013889 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 54.282407 Tz (such ) Tj 1.536111 0 Td 58.333333 Tz (an ) Tj 0.933333 0 Td 51.851852 Tz (end. ) Tj 1.516667 0 Td 48.905724 Tz (Ultimately, ) Tj 3.480556 0 Td 49.691358 Tz (the ) Tj 1.127778 0 Td 48.971193 Tz (inventive ) Tj 2.897222 0 Td 60.493827 Tz (method ) Tj 51.428571 0 0 51.428571 0 227.724656 Tm 25.316667 0 Td 51.041667 Tz (supplied ) Tj 2.702778 0 Td 51.851852 Tz (a ) Tj 0.563889 0 Td 56.388889 Tz (group ) Tj 1.925 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 46.843434 Tz (potentially ) Tj 3.363889 0 Td 46.450617 Tz (effective ) Tj 2.702778 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 46.018519 Tz (inhibitors ) Tj 3.013889 0 Td 50.231481 Tz (as ) Tj 51.428571 0 0 51.428571 0 176 Tm 25.297222 0 Td 48.935185 Tz (presented: ) Tj ET Q endstream endobj 200 0 obj << /Length 1 >> stream q endstream endobj 201 0 obj << /Length 4665 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 44.285714 0 0 44.285714 0 2595 Tm 7.790323 0 Td 117.921147 Tz (HOA ) Tj 49.285714 0 0 49.285714 0 2407.687943 Tm 9.028986 0 Td 81.835749 Tz (O=s=o ) Tj 4.565217 0 Td 67.63285 Tz (H ) Tj 31.428571 0 0 31.428571 0 2379 Tm 15.75 0 Td 111.363636 Tz (OH ) Tj 92.857143 0 0 92.857143 0 1528 Tm 5.955385 0 Td 37.692308 Tz (pi ) Tj 31.428571 0 0 31.428571 0 1491 Tm 15.431818 0 Td 205.492424 Tz (OSEO ) Tj 5.822727 0 Td 116.666667 Tz (N ) Tj 31.428571 0 0 31.428571 0 1424 Tm 21.222727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1291 Tm 21.222727 0 Td 114.015152 Tz (OH ) Tj 38.571429 0 0 38.571429 0 1119 Tm 12.807407 0 Td 74.897119 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 814 Tm 19.695455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 747 Tm 16.990909 0 Td 135.227273 Tz (HO-S ) Tj 31.428571 0 0 31.428571 0 681 Tm 19.695455 0 Td 111.363636 Tz (O ) Tj 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,343.934 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 14.661111 0 Td 71.296296 Tz (11 ) Tj 18.938889 0 Td 72.916667 Tz (12 ) Tj 38.571429 0 0 38.571429 0 2913 Tm 30.359259 0 Td 101.975309 Tz (TABLE ) Tj 3.37037 0 Td 64.814815 Tz (5 ) Tj 40 0 0 40 0 2814.146699 Tm 20.125 0 Td 56.25 Tz (Highly ) Tj 2.2 0 Td 51.388889 Tz (potent ) Tj 2 0 Td 76.388889 Tz (ATX ) Tj 1.6 0 Td 45.833333 Tz (inhibitors ) Tj 2.975 0 Td 45 Tz (identified ) Tj 2.9 0 Td 54.166667 Tz (through ) Tj 2.475 0 Td 48.611111 Tz (the ) Tj 1.025 0 Td 58.653846 Tz (pharmacophore ) Tj 4.725 0 Td 48.214286 Tz (screen. ) Tj 40 0 0 40 0 2716.197452 Tm 19.6 0 Td 67.1875 Tz (Compound ) Tj 3.425 0 Td 67.361111 Tz (Number ) Tj 2.575 0 Td 56.944444 Tz (and ) Tj 1.225 0 Td 49.537037 Tz (Structure ) Tj 14.4 0 Td 100 Tz (% ) Tj 0.75 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 46.759259 Tz (Acitivity ) Tj 2.725 0 Td 52.777778 Tz (\(10 ) Tj 1.5 0 Td 72.916667 Tz (M\) ) Tj 30 0 0 30 0 2625 Tm 58.333333 0 Td 77.777778 Tz (27 ) Tj 2 0 Td 64.814815 Tz (2.8 ) Tj 32.857143 0 0 32.857143 0 2554 Tm 29.582609 0 Td 68.478261 Tz (Cl ) Tj 2.647826 0 Td 106.521739 Tz (H ) Tj 31.428571 0 0 31.428571 0 2529 Tm 46.104545 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2504.522727 Tm 28.159091 0 Td 111.363636 Tz (O ) Tj 5.504545 0 Td 121.969697 Tz (N ) Tj 50 0 0 50 0 2475.006944 Tm 25.5 0 Td 76.666667 Tz (H ) Tj 2.48 0 Td 80.666667 Tz (OESEO ) Tj 31.428571 0 0 31.428571 0 2430 Tm 40.631818 0 Td 111.363636 Tz (N ) Tj 50 0 0 50 0 2391.804878 Tm 17.72 0 Td 66.666667 Tz (N ) Tj 3.44 0 Td 70 Tz (O ) Tj 32.380952 0 0 32.380952 0 2354 Tm 27.392647 0 Td 102.941176 Tz (H ) Tj 2.625 0 Td 69.485294 Tz (Cl ) Tj 7.998529 0 Td 108.088235 Tz (O ) Tj 40 0 0 40 0 2307 Tm 38.925 0 Td 87.5 Tz (n ) Tj 57.142857 0 0 57.142857 0 2286 Tm 26.6525 0 Td 49.583333 Tz (# ) Tj 0.9275 0 Td 67.083333 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2231 Tm 29.05 0 Td 100.757576 Tz (NSC ) Tj 2.131818 0 Td 74.242424 Tz (12859 ) Tj 30.952381 0 0 30.952381 0 1982.306569 Tm 35.7 0 Td 113.076923 Tz (O ) Tj 9.078462 0 Td 113.076923 Tz (O ) Tj 11.76 0 Td 102.307692 Tz (205.7 ) Tj 75.238095 0 0 75.238095 0 1929.571429 Tm 13.198101 0 Td 67.009494 Tz (Hos/ ) Tj 5.382911 0 Td 43.196203 Tz (\\, ) Tj 0.770886 0 Td 47.257384 Tz (-OH ) Tj 49.285714 0 0 49.285714 0 1891 Tm 21.324638 0 Td 71.014493 Tz (/ ) Tj 7.852174 0 Td 77.777778 Tz (\\ ) Tj 77.857143 0 0 77.857143 0 1867 Tm 13.447706 0 Td 68.501529 Tz (/ ) Tj 4.944954 0 Td 43.883792 Tz (\\, ) Tj 33.809524 0 0 33.809524 0 1722.777778 Tm 31.677465 0 Td 113.380282 Tz (N ) Tj 3.430986 0 Td 103.521127 Tz (OH ) Tj 3.430986 0 Td 85.446009 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 1063 Tm 29.05 0 Td 100.757576 Tz (NSC ) Tj 2.1 0 Td 75.30303 Tz (75779 ) Tj 30.714286 0 0 30.714286 0 811.596491 Tm 29.986047 0 Td 108.527132 Tz (H ) Tj 26.990698 0 Td 102.015504 Tz (394.3 ) Tj 41.428571 0 0 41.428571 0 773 Tm 21.844828 0 Td 64.367816 Tz (M ) Tj 31.428571 0 0 31.428571 0 748 Tm 28.159091 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 717 Tm 39.836364 0 Td 106.060606 Tz (H ) Tj 31.428571 0 0 31.428571 0 650 Tm 39.772727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 483 Tm 29.972727 0 Td 106.060606 Tz (HO ) Tj 40 0 0 40 0 280 Tm 28.8 0 Td 72.222222 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 224 Tm 29.304545 0 Td 100.757576 Tz (NSC ) Tj 2.068182 0 Td 78.219697 Tz (5014 ) Tj 41.428571 0 0 41.428571 0 2713 Tm 48.3 0 Td 50.287356 Tz (ICso ) Tj 1.4 0 Td 47.471264 Tz (\(LIM\) ) Tj 30 0 0 30 0 2625 Tm 67.566667 0 Td 71.111111 Tz (O.805 ) Tj 30 0 0 30 0 1982 Tm 67.633333 0 Td 66.666667 Tz (1.26 ) Tj 30 0 0 30 0 813 Tm 67.633333 0 Td 66.666667 Tz (1.27 ) Tj ET Q endstream endobj 202 0 obj << /Length 1 >> stream q endstream endobj 203 0 obj << /Length 3067 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 38.571429 0 0 38.571429 0 785 Tm 9.151852 0 Td 116.666667 Tz (ON ) Tj 31.428571 0 0 31.428571 0 2461 Tm 17.595455 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2088 Tm 19.631818 0 Td 108.712121 Tz (HO ) Tj 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,343.934 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.142857 0 0 52.142857 0 2968.5 Tm 14.441096 0 Td 73.515982 Tz (13 ) Tj 18.69863 0 Td 73.515982 Tz (14 ) Tj 40 0 0 40 0 2913 Tm 27.275 0 Td 97.5 Tz (TABLE ) Tj 3.175 0 Td 68.560606 Tz (5-continued ) Tj 40 0 0 40 0 2810.146699 Tm 20.125 0 Td 56.25 Tz (Highly ) Tj 2.2 0 Td 51.388889 Tz (potent ) Tj 2 0 Td 76.388889 Tz (ATX ) Tj 1.6 0 Td 45.833333 Tz (inhibitors ) Tj 2.975 0 Td 45 Tz (identified ) Tj 2.9 0 Td 54.166667 Tz (through ) Tj 2.475 0 Td 48.611111 Tz (the ) Tj 1.025 0 Td 58.653846 Tz (pharmacophore ) Tj 4.725 0 Td 48.214286 Tz (screen. ) Tj 40 0 0 40 0 2709.197452 Tm 19.6 0 Td 67.1875 Tz (Compound ) Tj 3.425 0 Td 67.361111 Tz (Number ) Tj 2.575 0 Td 56.944444 Tz (and ) Tj 1.225 0 Td 49.537037 Tz (Structure ) Tj 14.4 0 Td 100 Tz (% ) Tj 0.75 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 46.759259 Tz (Acitivity ) Tj 2.725 0 Td 52.777778 Tz (\(10 ) Tj 1.5 0 Td 72.916667 Tz (M\) ) Tj 69.047619 0 0 69.047619 0 2568.238095 Tm 11.977241 0 Td 125.517241 Tz (-k ) Tj 13.353103 0 Td 33.793103 Tz (43 ) Tj 0.868966 0 Td 28.965517 Tz (2.8 ) Tj 31.428571 0 0 31.428571 0 2528 Tm 25.55 0 Td 111.363636 Tz (O ) Tj 120 0 0 120 0 2441 Tm 5.733333 0 Td 161.111111 Tz (0 ) Tj 31.428571 0 0 31.428571 0 2428 Tm 23.163636 0 Td 106.060606 Tz (HN ) Tj 4.231818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2361 Tm 27.395455 0 Td 111.363636 Tz (O ) Tj 4.804545 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2304 Tm 29.018182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2261.655738 Tm 25.009091 0 Td 106.060606 Tz (HN ) Tj 4.804545 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2146 Tm 29.240909 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2088.666667 Tm 35.095455 0 Td 111.363636 Tz (NH ) Tj 4.263636 0 Td 111.363636 Tz (O ) Tj 35.714286 0 0 35.714286 0 1968.938462 Tm 34.636 0 Td 98 Tz (O ) Tj 7.476 0 Td 102.666667 Tz (NO ) Tj 31.428571 0 0 31.428571 0 1868 Tm 28.890909 0 Td 97.222222 Tz (NSC ) Tj 2.004545 0 Td 76.893939 Tz (341348 ) Tj 30.47619 0 0 30.47619 0 1168.25 Tm 29.892187 0 Td 114.84375 Tz (O ) Tj 27.529687 0 Td 76.5625 Tz (32 ) Tj 1.96875 0 Td 63.802083 Tz (2.7 ) Tj 81.428571 0 0 81.428571 0 1113 Tm 11.335088 0 Td 60.891813 Tz (\\-OH ) Tj 52.857143 0 0 52.857143 0 1077 Tm 18.086486 0 Td 88.288288 Tz (V ) Tj 31.428571 0 0 31.428571 0 1057 Tm 31.022727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 984 Tm 30.004545 0 Td 121.969697 Tz (N ) Tj 40 0 0 40 0 494 Tm 38.975 0 Td 72.222222 Tz (NH2 ) Tj 40 0 0 40 0 2707 Tm 50.025 0 Td 52.083333 Tz (ICso ) Tj 1.475 0 Td 60.416667 Tz (\(IM\) ) Tj 30 0 0 30 0 2619 Tm 67.8 0 Td 70.833333 Tz (2.50 ) Tj 30 0 0 30 0 1168 Tm 67.766667 0 Td 72.222222 Tz (4.07 ) Tj ET Q endstream endobj 204 0 obj << /Length 1 >> stream q endstream endobj 205 0 obj << /Length 21219 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,343.934 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.245946 0 Td 74.099099 Tz (15 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 32.691892 0 Td 72.522523 Tz (16 ) Tj 40 0 0 40 0 2913 Tm 27.275 0 Td 97.5 Tz (TABLE ) Tj 3.175 0 Td 68.560606 Tz (5-continued ) Tj 31.428571 0 0 31.428571 0 2851 Tm 25.645455 0 Td 68.939394 Tz (Highl ) Tj 31.428571 0 0 31.428571 0 2846.986985 Tm 28.890909 0 Td 62.575758 Tz (otent ) Tj 2.036364 0 Td 98.989899 Tz (ATX ) Tj 2.036364 0 Td 58.863636 Tz (inhibitors ) Tj 3.818182 0 Td 57.272727 Tz (identified ) Tj 3.659091 0 Td 68.939394 Tz (through ) Tj 3.15 0 Td 63.636364 Tz (the ) Tj 31.428571 0 0 31.428571 0 2849.373494 Tm 45.404545 0 Td 74.242424 Tz (harmacophore ) Tj 5.536364 0 Td 61.363636 Tz (screen. ) Tj 40 0 0 40 0 2776.069519 Tm 19.6 0 Td 67.1875 Tz (Compound ) Tj 3.425 0 Td 67.361111 Tz (Number ) Tj 2.575 0 Td 56.944444 Tz (and ) Tj 1.225 0 Td 49.537037 Tz (Structure ) Tj 40 0 0 40 0 2775.719101 Tm 41.225 0 Td 100 Tz (% ) Tj 0.75 0 Td 77.777778 Tz (ATX ) Tj 1.55 0 Td 47.222222 Tz (Acitivity ) Tj 2.8 0 Td 50 Tz (\(10 ) Tj 1.3 0 Td 56.944444 Tz (IM\) ) Tj 2.4 0 Td 55.555556 Tz (ICs ) Tj 1.5 0 Td 59.375 Tz (\(IM\) ) Tj 31.428571 0 0 31.428571 0 2621 Tm 20.363636 0 Td 111.363636 Tz (O ) Tj 8.622727 0 Td 111.363636 Tz (O ) Tj 72.380952 0 0 72.380952 0 2569.592593 Tm 7.336184 0 Td 67.351974 Tz (HOS/ ) Tj 5.429605 0 Td 42.598684 Tz (\\, ) Tj 0.773684 0 Td 47.587719 Tz (-OH ) Tj 46.428571 0 0 46.428571 0 2533 Tm 12.686154 0 Td 71.794872 Tz (M ) Tj 8.033846 0 Td 78.974359 Tz (M ) Tj 75.714286 0 0 75.714286 0 2509 Tm 7.726415 0 Td 66.037736 Tz (/ ) Tj 4.9 0 Td 44.025157 Tz (\\, ) Tj 31.428571 0 0 31.428571 0 2436 Tm 19.313636 0 Td 121.969697 Tz (N ) Tj 10.690909 0 Td 121.969697 Tz (N ) Tj 37.857143 0 0 37.857143 0 2367 Tm 16.033962 0 Td 101.257862 Tz (N ) Tj 2.958491 0 Td 76.310273 Tz (NH2 ) Tj 2.984906 0 Td 90.251572 Tz (OH ) Tj 2.958491 0 Td 96.855346 Tz (N ) Tj 38.571429 0 0 38.571429 0 2237 Tm 9.151852 0 Td 116.666667 Tz (ON ) Tj 31.428571 0 0 31.428571 0 2146 Tm 42.477273 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2081 Tm 42.477273 0 Td 121.969697 Tz (N ) Tj 40 0 0 40 0 1946 Tm 38.975 0 Td 72.222222 Tz (NH2 ) Tj 31.428571 0 0 31.428571 0 1911 Tm 39.645455 0 Td 111.363636 Tz (O ) Tj 81.428571 0 0 81.428571 0 1855 Tm 15.461404 0 Td 38.888889 Tz (\\, ) Tj 31.428571 0 0 31.428571 0 1838 Tm 39.9 0 Td 63.636364 Tz (1. ) Tj 50 0 0 50 0 1822 Tm 24.08 0 Td 96.666667 Tz (HO1V ) Tj 75.714286 0 0 75.714286 0 1799 Tm 17.064151 0 Td 45.125786 Tz (\\, ) Tj 31.428571 0 0 31.428571 0 1744 Tm 29.081818 0 Td 98.989899 Tz (NSC ) Tj 2.036364 0 Td 76.363636 Tz (75520 ) Tj 30 0 0 30 0 1507 Tm 41.6 0 Td 77.777778 Tz (35 ) Tj 51.428571 0 0 51.428571 0 1460.01107 Tm 7.097222 0 Td 57.685185 Tz (These ) Tj 1.847222 0 Td 62.294239 Tz (compounds ) Tj 3.519444 0 Td 53.148148 Tz (noted ) Tj 1.711111 0 Td 57.685185 Tz (above ) Tj 1.866667 0 Td 48.148148 Tz (exhibit ) Tj 2.119444 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 50.05144 Tz (reduction ) Tj 2.858333 0 Td 46.990741 Tz (in ) Tj 0.661111 0 Td 68.055556 Tz (ATX- ) Tj 3.830556 0 Td 55.092593 Tz (Coupled, ) Tj 2.761111 0 Td 48.070988 Tz (again, ) Tj 1.905556 0 Td 51.851852 Tz (with ) Tj 1.380556 0 Td 49.691358 Tz (the ) Tj 1.011111 0 Td 45.37037 Tz (oral ) Tj 1.244444 0 Td 46.234568 Tz (bioavailability ) Tj 4.277778 0 Td 46.234568 Tz (characteristics ) Tj 51.428571 0 0 51.428571 0 1407.489493 Tm 6.358333 0 Td 51.131687 Tz (catalyzed ) Tj 3.033333 0 Td 56.712963 Tz (FS-3 ) Tj 1.633333 0 Td 50.555556 Tz (hydrolysis ) Tj 3.286111 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 45.910494 Tz (target ) Tj 1.905556 0 Td 58.981481 Tz (tumor ) Tj 1.983333 0 Td 44.722222 Tz (cells ) Tj 1.594444 0 Td 59.953704 Tz (by ) Tj 0.991667 0 Td 72.376543 Tz (54% ) Tj 1.575 0 Td 53.472222 Tz (or ) Tj 2.080556 0 Td 53.796296 Tz (noted ) Tj 1.769444 0 Td 52.932099 Tz (above, ) Tj 2.061111 0 Td 50.555556 Tz (these ) Tj 1.691667 0 Td 61.574074 Tz (compounds ) Tj 3.5 0 Td 54.282407 Tz (hold ) Tj 1.438889 0 Td 48.611111 Tz (great ) Tj 1.633333 0 Td 56.018519 Tz (promise ) Tj 2.508333 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 59.41358 Tz (provid ) Tj 62.857143 0 0 62.857143 0 1346.625475 Tm 5.202273 0 Td 51.704545 Tz (more ) Tj 1.352273 0 Td 39.772727 Tz (at ) Tj 0.572727 0 Td 47.727273 Tz (a ) Tj 0.445455 0 Td 41.200466 Tz (concentration ) Tj 3.356818 0 Td 46.401515 Tz (of ) Tj 0.636364 0 Td 45.075758 Tz (about ) Tj 1.527273 0 Td 43.75 Tz (10 ) Tj 0.986364 0 Td 54.356061 Tz (M. ) Tj 0.795455 0 Td 49.715909 Tz (Such ) Tj 1.352273 0 Td 45.075758 Tz (a ) Tj 0.413636 0 Td 41.245791 Tz (reduction ) Tj 2.402273 0 Td 37.121212 Tz (in ) Tj 1.670455 0 Td 40.656566 Tz (ing ) Tj 0.906818 0 Td 38.005051 Tz (orally ) Tj 1.527273 0 Td 40.568182 Tz (ingestable ) Tj 2.545455 0 Td 48.787879 Tz (tumor ) Tj 1.575 0 Td 41.363636 Tz (treatments ) Tj 2.672727 0 Td 37.121212 Tz (for ) Tj 0.811364 0 Td 38.257576 Tz (certain ) Tj 1.765909 0 Td 39.772727 Tz (cancers. ) Tj 59.627329 0 0 59.627329 0 1297.333333 Tm 5.484062 0 Td 39.131944 Tz (activity ) Tj 1.978958 0 Td 48.914931 Tz (of ) Tj 0.687604 0 Td 43.479938 Tz (autotaxin ) Tj 2.482083 0 Td 33.541667 Tz (is ) Tj 0.553437 0 Td 40.99537 Tz (basically ) Tj 2.364687 0 Td 40.529514 Tz (in ) Tj 0.620521 0 Td 46.399306 Tz (terms ) Tj 1.526146 0 Td 44.722222 Tz (of ) Tj 0.654062 0 Td 40.063657 Tz (potential ) Tj 2.331146 0 Td 44.322917 Tz (conver- ) Tj 2.230521 0 Td 43.324653 Tz (40 ) Tj 1.542917 0 Td 55.902778 Tz (AS ) Tj 0.805 0 Td 44.322917 Tz (alluded ) Tj 1.978958 0 Td 37.734375 Tz (to ) Tj 0.570208 0 Td 45.653935 Tz (above, ) Tj 1.744167 0 Td 43.324653 Tz (as ) Tj 0.670833 0 Td 40.25 Tz (well, ) Tj 1.341667 0 Td 29.348958 Tz (it ) Tj 0.452812 0 Td 33.541667 Tz (is ) Tj 0.536667 0 Td 43.674045 Tz (believed ) Tj 2.21375 0 Td 38.43316 Tz (that ) Tj 1.056562 0 Td 42.858796 Tz (the ) Tj 0.872083 0 Td 40.374228 Tz (differing ) Tj 51.428571 0 0 51.428571 0 1245.097561 Tm 6.377778 0 Td 49.421296 Tz (sion ) Tj 1.4 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 71.296296 Tz (LPC ) Tj 1.536111 0 Td 43.75 Tz (to ) Tj 0.797222 0 Td 60.763889 Tz (LPA, ) Tj 1.652778 0 Td 46.720679 Tz (particularly ) Tj 3.616667 0 Td 53.703704 Tz (through ) Tj 2.488889 0 Td 45.37037 Tz (structural ) Tj 2.955556 0 Td 50.462963 Tz (modifi- ) Tj 3.597222 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 49.259259 Tz (exhibiting ) Tj 3.15 0 Td 49.074074 Tz (similar ) Tj 2.236111 0 Td 54.282407 Tz (base ) Tj 1.497222 0 Td 49.907407 Tz (point ) Tj 1.730556 0 Td 46.666667 Tz (structures ) Tj 3.013889 0 Td 54.62963 Tz (through ) Tj 57.815126 0 0 57.815126 0 1183.730817 Tm 5.655959 0 Td 43.653101 Tz (cations ) Tj 2.023692 0 Td 40.358527 Tz (to ) Tj 0.639971 0 Td 46.535853 Tz (prevent ) Tj 2.092878 0 Td 49.9677 Tz (placement ) Tj 2.836628 0 Td 53.330911 Tz (of ) Tj 0.726453 0 Td 45.163114 Tz (the ) Tj 1.003198 0 Td 64.38146 Tz (LPC ) Tj 1.331831 0 Td 56.934351 Tz (compound ) Tj 2.92311 0 Td 41.079215 Tz (into ) Tj 1.176163 0 Td 44.202196 Tz (the ) Tj 2.075581 0 Td 45.163114 Tz (the ) Tj 1.072384 0 Td 51.889535 Tz (pharmacophore ) Tj 4.341424 0 Td 49.268851 Tz (comparisons ) Tj 3.528488 0 Td 42.417636 Tz (herein, ) Tj 2.075581 0 Td 63.420543 Tz (may ) Tj 1.418314 0 Td 42.520591 Tz (also ) Tj 1.331831 0 Td 42.829457 Tz (exhibit ) Tj 51.428571 0 0 51.428571 0 1136.261294 Tm 6.358333 0 Td 47.530864 Tz (active ) Tj 1.866667 0 Td 42.12963 Tz (site ) Tj 1.166667 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 47.530864 Tz (the ) Tj 1.05 0 Td 53.472222 Tz (modified ) Tj 2.702778 0 Td 50.05144 Tz (autotaxin ) Tj 2.858333 0 Td 57.87037 Tz (enzyme. ) Tj 2.605556 0 Td 58.333333 Tz (These ) Tj 1.925 0 Td 52.256944 Tz (naphtha- ) Tj 3.986111 0 Td 46.090535 Tz (effective ) Tj 2.8 0 Td 47.43266 Tz (synergistic ) Tj 3.422222 0 Td 45.730453 Tz (qualities ) Tj 2.780556 0 Td 45.37037 Tz (in ) Tj 0.836111 0 Td 52.572016 Tz (providing ) Tj 3.15 0 Td 46.450617 Tz (differing ) Tj 2.819444 0 Td 45.910494 Tz (levels ) Tj 54.285714 0 0 54.285714 0 1093.504028 Tm 22.971053 0 Td 42.982456 Tz (as ) Tj 0.994737 0 Td 49.634503 Tz (and/or ) Tj 1.897368 0 Td 50 Tz (degrees ) Tj 2.247368 0 Td 50.657895 Tz (of ) Tj 0.7 0 Td 71.637427 Tz (ATX ) Tj 1.455263 0 Td 44.824561 Tz (inhibition ) Tj 2.836842 0 Td 61.403509 Tz (when ) Tj 1.621053 0 Td 42.982456 Tz (utilized ) Tj 2.210526 0 Td 47.587719 Tz (as ) Tj 0.7 0 Td 48.508772 Tz (prescribed ) Tj 51.428571 0 0 51.428571 0 1066.268507 Tm 6.358333 0 Td 51.041667 Tz (lene ) Tj 1.497222 0 Td 49.421296 Tz (sulfones ) Tj 2.683333 0 Td 37.808642 Tz (\(first ) Tj 1.613889 0 Td 59.41358 Tz (two ) Tj 1.361111 0 Td 50 Tz (above\), ) Tj 2.391667 0 Td 52.314815 Tz (phenylsulfones ) Tj 4.666667 0 Td 49.907407 Tz (\(next ) Tj 1.75 0 Td 49.259259 Tz (two\), ) Tj 51.428571 0 0 51.428571 0 1044.523688 Tm 25.297222 0 Td 51.851852 Tz (above. ) Tj 2.138889 0 Td 68.055556 Tz (As ) Tj 1.108333 0 Td 49.907407 Tz (such, ) Tj 1.808333 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 47.170782 Tz (potential ) Tj 2.858333 0 Td 47.530864 Tz (for ) Tj 1.127778 0 Td 47.685185 Tz (further ) Tj 2.255556 0 Td 57.523148 Tz (improvements ) Tj 4.433333 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 999.743149 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.380556 0 Td 50.231481 Tz (peptides ) Tj 2.761111 0 Td 53.472222 Tz (with ) Tj 1.652778 0 Td 50.411523 Tz (unnatural ) Tj 3.033333 0 Td 60.925926 Tz (amino ) Tj 2.158333 0 Td 49.259259 Tz (acids ) Tj 1.847222 0 Td 42.12963 Tz (\(last ) Tj 1.555556 0 Td 50.555556 Tz (two\), ) Tj 1.847222 0 Td 51.041667 Tz (thus ) Tj 2.702778 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 57.87037 Tz (methods ) Tj 2.663889 0 Td 68.055556 Tz (may ) Tj 1.438889 0 Td 58.333333 Tz (be ) Tj 0.894444 0 Td 48.251029 Tz (available ) Tj 2.819444 0 Td 53.240741 Tz (through ) Tj 2.45 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 47.314815 Tz (utili ) Tj 51.428571 0 0 51.428571 0 947.544506 Tm 6.358333 0 Td 48.148148 Tz (exhibit ) Tj 2.197222 0 Td 48.611111 Tz (excellent ) Tj 2.780556 0 Td 78.858025 Tz (ATX ) Tj 1.613889 0 Td 46.990741 Tz (inhibition ) Tj 3.013889 0 Td 47.138047 Tz (properties, ) Tj 3.305556 0 Td 58.981481 Tz (which ) Tj 2.002778 0 Td 49.421296 Tz (thus ) Tj 1.380556 0 Td 48.611111 Tz (cor- ) Tj 2.644444 0 Td 49.151235 Tz (Zation ) Tj 1.963889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 54.282407 Tz (Such ) Tj 1.516667 0 Td 54.012346 Tz (combinations ) Tj 4.083333 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 58.657407 Tz (compounds. ) Tj 52.857143 0 0 52.857143 0 891.445062 Tm 6.186486 0 Td 41.441441 Tz (relate, ) Tj 1.92973 0 Td 52.027027 Tz (with ) Tj 1.475676 0 Td 47.297297 Tz (the ) Tj 1.059459 0 Td 46.981982 Tz (Lipinski's ) Tj 3.045946 0 Td 44.144144 Tz (rules ) Tj 1.513514 0 Td 40.640641 Tz (criteria, ) Tj 2.402703 0 Td 44.144144 Tz (to ) Tj 0.7 0 Td 45.864046 Tz (potentially ) Tj 3.216216 0 Td 45.720721 Tz (effec- ) Tj 2.081081 0 Td 40.990991 Tz (so ) Tj 1.683784 0 Td 55.495495 Tz (There ) Tj 1.891892 0 Td 44.144144 Tz (are, ) Tj 1.286486 0 Td 58.333333 Tz (of ) Tj 0.832432 0 Td 47.747748 Tz (course, ) Tj 2.27027 0 Td 63.063063 Tz (many ) Tj 1.759459 0 Td 45.004095 Tz (alternative ) Tj 3.178378 0 Td 57.903358 Tz (embodiments ) Tj 4.067568 0 Td 57.807808 Tz (and ) Tj 51.428571 0 0 51.428571 0 839.062461 Tm 6.338889 0 Td 45.37037 Tz (tive ) Tj 1.4 0 Td 45.910494 Tz (orally ) Tj 1.963889 0 Td 49.259259 Tz (ingestable ) Tj 3.247222 0 Td 50.231481 Tz (treatments ) Tj 3.325 0 Td 48.611111 Tz (for ) Tj 1.186111 0 Td 49.074074 Tz (various ) Tj 2.372222 0 Td 47.685185 Tz (patient ) Tj 2.275 0 Td 46.990741 Tz (types, ) Tj 3.188889 0 Td 50.605413 Tz (modifications ) Tj 4.141667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 50 Tz (present ) Tj 2.275 0 Td 50.411523 Tz (invention ) Tj 2.897222 0 Td 58.981481 Tz (which ) Tj 1.963889 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 52.256944 Tz (intended ) Tj 2.683333 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 785.06298 Tm 6.358333 0 Td 46.450617 Tz (particularly ) Tj 3.538889 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 53.472222 Tz (cancer ) Tj 2.061111 0 Td 45.010288 Tz (patients. ) Tj 10.130556 0 Td 61.574074 Tz (be ) Tj 0.894444 0 Td 52.256944 Tz (included ) Tj 2.683333 0 Td 51.311728 Tz (within ) Tj 2.041667 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 41.049383 Tz (spirit ) Tj 1.633333 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 55.092593 Tz (scope ) Tj 1.827778 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 42.939815 Tz (this ) Tj 1.244444 0 Td 47.314815 Tz (invention. ) Tj 47.619048 0 0 47.619048 0 732.305201 Tm 7.665 0 Td 67.666667 Tz (The ) Tj 1.449 0 Td 59.5 Tz (term ) Tj 1.701 0 Td 56.954545 Tz (napthalene ) Tj 3.99 0 Td 55.125 Tz (sulfone' ) Tj 2.898 0 Td 43.75 Tz (is ) Tj 0.798 0 Td 56 Tz (intended ) Tj 2.919 0 Td 50.75 Tz (to ) Tj 0.861 0 Td 63.777778 Tz (encompass ) Tj 5.817 0 Td 71.75 Tz (What ) Tj 1.911 0 Td 77 Tz (we ) Tj 1.092 0 Td 58.1 Tz (claim ) Tj 1.953 0 Td 38.5 Tz (is: ) Tj 60.285714 0 0 60.285714 0 676.748564 Tm 5.424171 0 Td 48.841496 Tz (any ) Tj 1.061611 0 Td 54.601106 Tz (compound ) Tj 2.803318 0 Td 43.00509 Tz (including ) Tj 2.488152 0 Td 46.99842 Tz (a ) Tj 0.464455 0 Td 45.239121 Tz (naphthalene ) Tj 3.135071 0 Td 51.606108 Tz (and ) Tj 1.061611 0 Td 46.99842 Tz (a ) Tj 0.464455 0 Td 43.048973 Tz (Sulfone ) Tj 1.973934 0 Td 48.657188 Tz (group ) Tj 1.841232 0 Td 37.322275 Tz (55 ) Tj 1.492891 0 Td 35.939968 Tz (1. ) Tj 0.663507 0 Td 82.938389 Tz (A ) Tj 0.746445 0 Td 52.527646 Tz (method ) Tj 2.156398 0 Td 41.469194 Tz (for ) Tj 0.978673 0 Td 40.086888 Tz (treating ) Tj 2.189573 0 Td 46.99842 Tz (a ) Tj 0.563981 0 Td 40.28436 Tz (patient ) Tj 1.957346 0 Td 40.086888 Tz (to ) Tj 0.729858 0 Td 47.459189 Tz (reduce ) Tj 1.973934 0 Td 43.00509 Tz (autotaxin ) Tj 51.428571 0 0 51.428571 0 631.001785 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 46.990741 Tz (that ) Tj 1.302778 0 Td 55.902778 Tz (comports ) Tj 2.877778 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 47.890947 Tz (six-point ) Tj 2.722222 0 Td 58.582621 Tz (pharmacophore ) Tj 4.725 0 Td 43.344907 Tz (criteria ) Tj 3.538889 0 Td 44.965278 Tz (activity ) Tj 2.294444 0 Td 51.311728 Tz (within ) Tj 1.963889 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 48.611111 Tz (subject ) Tj 2.158333 0 Td 46.090535 Tz (patients ) Tj 2.605556 0 Td 53.796296 Tz (body, ) Tj 1.730556 0 Td 49.421296 Tz (said ) Tj 1.322222 0 Td 59.41358 Tz (method ) Tj 2.294444 0 Td 56.712963 Tz (involv ) Tj 46.616541 0 0 46.616541 0 580.969183 Tm 11.047581 0 Td 44.69086 Tz (ts ) Tj 0.815161 0 Td 50.053763 Tz (set ) Tj 1.136935 0 Td 51.483871 Tz (forth ) Tj 1.823387 0 Td 60.77957 Tz (ab ) Tj 2.359677 0 Td 56.807049 Tz (Likewise, ) Tj 3.367903 0 Td 53.629032 Tz (the ) Tj 1.244194 0 Td 35.752688 Tz (t ) Tj 1.694677 0 Td 59.758065 Tz (phenvl ) Tj 4.419032 0 Td 56.012545 Tz (ing ) Tj 1.222742 0 Td 54.820789 Tz (the ) Tj 1.20129 0 Td 53.926971 Tz (introduction ) Tj 4.097258 0 Td 56.012545 Tz (within ) Tj 2.252419 0 Td 54.820789 Tz (the ) Tj 1.20129 0 Td 53.629032 Tz (Subject ) Tj 2.424032 0 Td 52.607527 Tz (patient ) Tj 2.424032 0 Td 62.567204 Tz (of ) Tj 0.836613 0 Td 50.053763 Tz (at ) Tj 0.772258 0 Td 50.053763 Tz (least ) Tj 1.673226 0 Td 65.546595 Tz (one ) Tj 35.714286 0 0 35.714286 0 561.721584 Tm 9.156 0 Td 83.222222 Tz (measuremenus ) Tj 6.328 0 Td 60.666667 Tz (Set ) Tj 1.54 0 Td 65.333333 Tz (Torun ) Tj 2.296 0 Td 75.444444 Tz (above. ) Tj 3.164 0 Td 73.111111 Tz (L1KeW1Se, ) Tj 4.312 0 Td 53.666667 Tz (line ) Tj 1.708 0 Td 73.5 Tz (term ) Tj 2.632 0 Td 87.888889 Tz (phenyl ) Tj 48.87218 0 0 48.87218 0 525.456024 Tm 6.711385 0 Td 53.285256 Tz (Sulfone' ) Tj 2.721385 0 Td 40.923077 Tz (is ) Tj 0.675231 0 Td 54.564103 Tz (intended ) Tj 2.741846 0 Td 49.448718 Tz (to ) Tj 0.716154 0 Td 62.521368 Tz (encompass ) Tj 3.498923 0 Td 60.247863 Tz (anV ) Tj 1.289077 0 Td 67.352564 Tz (compound ) Tj 3.335231 0 Td 162.555556 Tz (Mr. ) Tj 3.069231 0 Td 47.74359 Tz (a ) Tj 1.862 0 Td 67.352564 Tz (compound ) Tj 3.437538 0 Td 51.153846 Tz (selected ) Tj 2.66 0 Td 59.679487 Tz (from ) Tj 1.616462 0 Td 53.42735 Tz (the ) Tj 1.145846 0 Td 60.020513 Tz (group ) Tj 1.984769 0 Td 51.494872 Tz (consisting ) Tj 3.294308 0 Td 59.679487 Tz (of ) Tj 0.798 0 Td 47.74359 Tz (at ) Tj 0.757077 0 Td 47.061538 Tz (least ) Tj 1.575538 0 Td 62.521368 Tz (one ) Tj 51.530612 0 0 51.530612 0 486.560924 Tm 14.806733 0 Td 71.155116 Tz (p ) Tj 2.05703 0 Td 64.686469 Tz (y ) Tj 1.746535 0 Td 61.452145 Tz (p ) Tj 4.346931 0 Td 27.491749 Tz (9. ) Tj 1.280792 0 Td 45.280528 Tz (60 ) Tj 1.009109 0 Td 53.219322 Tz (naphthalene ) Tj 3.628911 0 Td 48.110561 Tz (Sulfone, ) Tj 2.445149 0 Td 43.663366 Tz (at ) Tj 0.640396 0 Td 44.633663 Tz (least ) Tj 1.455446 0 Td 58.217822 Tz (one ) Tj 1.14495 0 Td 51.056106 Tz (phenylsulfone, ) Tj 4.424554 0 Td 57.139714 Tz (and ) Tj 1.14495 0 Td 57.139714 Tz (any ) Tj 1.203168 0 Td 74.389439 Tz (mix ) Tj 48.571429 0 0 48.571429 0 450.937313 Tm 6.732353 0 Td 55.957768 Tz (phenylsulfone ) Tj 4.673529 0 Td 60.392157 Tz (group ) Tj 2.161765 0 Td 59.019608 Tz (comporting ) Tj 3.891176 0 Td 55.759804 Tz (with ) Tj 1.667647 0 Td 54.901961 Tz (the ) Tj 1.317647 0 Td 61.500754 Tz (pharmacophore ) Tj 6.320588 0 Td 50.098039 Tz (tures ) Tj 1.708824 0 Td 48.897059 Tz (thereof. ) Tj 45.465839 0 0 45.465839 0 389.239446 Tm 7.214208 0 Td 52.949808 Tz (structure ) Tj 3.123224 0 Td 51.320583 Tz (in ) Tj 0.901776 0 Td 61.401412 Tz (such ) Tj 1.693579 0 Td 62.317851 Tz (a ) Tj 0.659836 0 Td 61.794171 Tz (manner. ) Tj 2.837295 0 Td 73.315118 Tz (As ) Tj 1.143716 0 Td 53.520036 Tz (well, ) Tj 1.89153 0 Td 54.986339 Tz (the ) Tj 1.253689 0 Td 61.401412 Tz (term ) Tj 1.737568 0 Td 58.193875 Tz ("peptide ) Tj 3.05724 0 Td 61.401412 Tz (with ) Tj 3.915027 0 Td 49.487705 Tz (2. ) Tj 0.835792 0 Td 72.0932 Tz (The ) Tj 1.583607 0 Td 67.816485 Tz (method ) Tj 2.683333 0 Td 64.150729 Tz (of ) Tj 0.92377 0 Td 60.118397 Tz (claim ) Tj 2.111475 0 Td 51.320583 Tz (1 ) Tj 0.615847 0 Td 62.84153 Tz (wherein ) Tj 2.925273 0 Td 54.0699 Tz (said ) Tj 1.517623 0 Td 53.153461 Tz (at ) Tj 0.857787 0 Td 51.320583 Tz (least ) Tj 1.781557 0 Td 65.983607 Tz (one ) Tj 1.40765 0 Td 94.087735 Tz (com ) Tj 51.428571 0 0 51.428571 0 334.129927 Tm 6.338889 0 Td 50.771605 Tz (unnatural ) Tj 2.994444 0 Td 60.277778 Tz (amino ) Tj 2.041667 0 Td 50.771605 Tz (acids ) Tj 2.041667 0 Td 38.888889 Tz (is ) Tj 0.719444 0 Td 52.256944 Tz (intended ) Tj 2.722222 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 58.693416 Tz (encompass ) Tj 3.402778 0 Td 57.253086 Tz (any ) Tj 1.263889 0 Td 62.384259 Tz (com- ) Tj 2.975 0 Td 60.925926 Tz (pound ) Tj 2.002778 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 1.497222 0 Td 59.41358 Tz (one ) Tj 1.263889 0 Td 53.030303 Tz (naphthalene ) Tj 3.675 0 Td 47.800926 Tz (Sulfone. ) Tj 50.408163 0 0 50.408163 0 279.514715 Tm 6.487045 0 Td 62.159244 Tz (pound ) Tj 2.063158 0 Td 52.166742 Tz (including ) Tj 2.995547 0 Td 59.51417 Tz (a ) Tj 0.575304 0 Td 51.956815 Tz (peptide ) Tj 2.400405 0 Td 56.869096 Tz (group ) Tj 1.94413 0 Td 59.51417 Tz (and ) Tj 1.289474 0 Td 53.137652 Tz (simultaneously ) Tj 4.681781 0 Td 62.159244 Tz (amino ) Tj 2.340891 0 Td 44.635628 Tz (65 ) Tj 1.765587 0 Td 44.635628 Tz (3. ) Tj 0.734008 0 Td 66.126856 Tz (The ) Tj 1.42834 0 Td 60.616284 Tz (method ) Tj 2.380567 0 Td 61.167341 Tz (of ) Tj 0.833198 0 Td 54.224022 Tz (claim ) Tj 1.844939 0 Td 59.51417 Tz (2 ) Tj 0.61498 0 Td 55.735493 Tz (wherein ) Tj 2.578947 0 Td 49.595142 Tz (said ) Tj 1.388664 0 Td 47.94197 Tz (at ) Tj 0.753846 0 Td 45.62753 Tz (least ) Tj 1.567206 0 Td 59.51417 Tz (one ) Tj 1.309312 0 Td 68.606613 Tz (naph ) Tj 51.428571 0 0 51.428571 0 224.461538 Tm 6.358333 0 Td 49.259259 Tz (acids ) Tj 1.711111 0 Td 57.79321 Tz (formed ) Tj 2.275 0 Td 53.703704 Tz (through ) Tj 2.45 0 Td 48.971193 Tz (synthetic ) Tj 2.838889 0 Td 48.611111 Tz (routes ) Tj 1.944444 0 Td 48.148148 Tz (therein ) Tj 2.216667 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 46.990741 Tz (that ) Tj 1.302778 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 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Tm 14.245946 0 Td 74.099099 Tz (19 ) Tj 18.389189 0 Td 77.252252 Tz (20 ) Tj 40 0 0 40 0 2871 Tm 8.175 0 Td 64.583333 Tz (A\) ) Tj 31.428571 0 0 31.428571 0 2818 Tm 14 0 Td 111.363636 Tz (O ) Tj 70.714286 0 0 70.714286 0 2769.444444 Tm 4.638384 0 Td 40.06734 Tz (HO- ) Tj 1.230303 0 Td 35.353535 Tz (4. ) Tj 37.142857 0 0 37.142857 0 2725.563218 Tm 10.419231 0 Td 112.179487 Tz (M ) Tj 11.388462 0 Td 94.230769 Tz (O ) Tj 9.369231 0 Td 94.230769 Tz (C ) Tj 3.123077 0 Td 89.74359 Tz (H ) Tj 31.428571 0 0 31.428571 0 2696 Tm 11.868182 0 Td 111.363636 Tz (O ) Tj 45.181818 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2660 Tm 33.122727 0 Td 111.363636 Tz (O ) Tj 7.381818 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2627 Tm 23.959091 0 Td 121.969697 Tz (N ) Tj 25.804545 0 Td 106.060606 Tz (H ) Tj 5.154545 0 Td 164.393939 Tz (OESEO ) Tj 31.428571 0 0 31.428571 0 2560 Tm 14.477273 0 Td 164.393939 Tz (OESEO ) Tj 9.545455 0 Td 106.060606 Tz (H ) Tj 25.677273 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2527 Tm 33.122727 0 Td 121.969697 Tz (N ) Tj 7.35 0 Td 116.666667 Tz (O ) Tj 31.428571 0 0 31.428571 0 2490 Tm 16.609091 0 Td 111.363636 Tz (OH ) Tj 45.181818 0 Td 111.363636 Tz (O ) Tj 37.142857 0 0 37.142857 0 2456.551724 Tm 28.080769 0 Td 89.74359 Tz (H ) Tj 3.096154 0 Td 94.230769 Tz (C ) Tj 9.315385 0 Td 94.230769 Tz (O ) Tj 11.253846 0 Td 112.179487 Tz (M ) Tj 31.428571 0 0 31.428571 0 2427 Tm 60.836364 0 Td 74.242424 Tz (S ) Tj 57.142857 0 0 57.142857 0 2393 Tm 33.04 0 Td 88.229167 Tz (/NOH ) Tj 77.142857 0 0 77.142857 0 2369 Tm 24.422222 0 Td 69.135802 Tz (/ ) Tj 40 0 0 40 0 2225 Tm 8.25 0 Td 56.25 Tz (B\) ) Tj 31.428571 0 0 31.428571 0 2173 Tm 31.372727 0 Td 111.363636 Tz (O ) Tj 8.909091 0 Td 116.666667 Tz (O ) Tj 74.761905 0 0 74.761905 0 2119.540541 Tm 11.690446 0 Td 67.436306 Tz (Hos/ ) Tj 5.430573 0 Td 42.356688 Tz (\\, ) Tj 0.775796 0 Td 46.815287 Tz (-OH ) Tj 50 0 0 50 0 2081 Tm 18.66 0 Td 70 Tz (M ) Tj 7.74 0 Td 76.666667 Tz (\\ ) Tj 77.857143 0 0 77.857143 0 2057 Tm 11.93211 0 Td 68.501529 Tz (/ ) Tj 4.93211 0 Td 44.954128 Tz (\\, ) Tj 31.428571 0 0 31.428571 0 1982 Tm 30.322727 0 Td 121.969697 Tz (N ) Tj 34.285714 0 0 34.285714 0 1912.333333 Tm 27.795833 0 Td 111.805556 Tz (N ) Tj 3.383333 0 Td 102.083333 Tz (OH ) Tj 3.354167 0 Td 84.259259 Tz (NH2 ) Tj 91.428571 0 0 91.428571 0 1719 Tm 4.757812 0 Td 38.28125 Tz (pi ) Tj 32.857143 0 0 32.857143 0 1681 Tm 11.169565 0 Td 156.231884 Tz (OESEO ) Tj 5.569565 0 Td 111.594203 Tz (N ) Tj 57.142857 0 0 57.142857 0 1638 Tm 9.6775 0 Td 37.916667 Tz (| ) Tj 31.428571 0 0 31.428571 0 1614 Tm 17.468182 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1480 Tm 17.468182 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 1308 Tm 9.375 0 Td 73.611111 Tz (NH2 ) Tj 40 0 0 40 0 1168.573021 Tm 9.125 0 Td 52.083333 Tz (9. ) Tj 0.925 0 Td 83.333333 Tz (The ) Tj 1.8 0 Td 77.083333 Tz (method ) Tj 3.05 0 Td 72.916667 Tz (of ) Tj 1.05 0 Td 68.333333 Tz (claim ) Tj 2.4 0 Td 66.666667 Tz (6 ) Tj 0.7 0 Td 71.428571 Tz (wherein ) Tj 3.325 0 Td 61.458333 Tz (said ) Tj 1.725 0 Td 60.416667 Tz (at ) Tj 1 0 Td 57.5 Tz (least ) Tj 2 0 Td 75 Tz (one ) Tj 1.6 0 Td 80.208333 Tz (com- ) Tj 13.125 0 Td 66.666667 Tz (-continued ) Tj 49.795918 0 0 49.795918 0 1124.833977 Tm 6.566803 0 Td 62.923497 Tz (pound ) Tj 2.068443 0 Td 40.163934 Tz (is ) Tj 0.682787 0 Td 46.857923 Tz (at ) Tj 0.743033 0 Td 46.188525 Tz (least ) Tj 1.566393 0 Td 60.245902 Tz (one ) Tj 1.265164 0 Td 52.356557 Tz (phenylsulfone. ) Tj 13.234016 0 Td 50.204918 Tz (D\) ) Tj 51.428571 0 0 51.428571 0 1079.678663 Tm 7.136111 0 Td 46.450617 Tz (10. ) Tj 1.030556 0 Td 64.814815 Tz (The ) Tj 1.4 0 Td 59.41358 Tz (method ) Tj 2.333333 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 53.148148 Tz (claim ) Tj 1.788889 0 Td 61.574074 Tz (9 ) Tj 0.602778 0 Td 55.092593 Tz (wherein ) Tj 2.527778 0 Td 49.421296 Tz (said ) Tj 1.380556 0 Td 43.75 Tz (at ) Tj 0.719444 0 Td 45.37037 Tz (least ) Tj 1.536111 0 Td 59.41358 Tz (one ) Tj 1.263889 0 Td 53.472222 Tz (phe- ) Tj 1.711111 0 Td 46.990741 Tz (45 ) Tj 51.428571 0 0 51.428571 0 1040.304982 Tm 6.358333 0 Td 51.527778 Tz (nylsulfone ) Tj 3.266667 0 Td 55.740741 Tz (meets ) Tj 1.866667 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 46.8107 Tz (structure ) Tj 2.702778 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 45.37037 Tz (at ) Tj 0.738889 0 Td 44.074074 Tz (least ) Tj 1.497222 0 Td 58.333333 Tz (one ) Tj 1.225 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 65.174897 Tz (Compounds ) Tj 40 0 0 40 0 1004 Tm 8.175 0 Td 104.166667 Tz (C ) Tj 0.85 0 Td 75 Tz (and ) Tj 1.625 0 Td 70.833333 Tz (D: ) Tj 40 0 0 40 0 876 Tm 8.2 0 Td 58.333333 Tz (C\) ) Tj 31.428571 0 0 31.428571 0 777 Tm 13.809091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 768 Tm 22.813636 0 Td 106.060606 Tz (H ) Tj 37.142857 0 0 37.142857 0 739 Tm 18.926923 0 Td 62.820513 Tz (M ) Tj 31.428571 0 0 31.428571 0 714 Tm 11.2 0 Td 131.25 Tz (HO-S ) Tj 10.563636 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 685 Tm 32.677273 0 Td 106.060606 Tz (H ) Tj 31.428571 0 0 31.428571 0 652 Tm 13.809091 0 Td 111.363636 Tz (O ) Tj 102.857143 0 0 102.857143 0 529.992308 Tm 8.497222 0 Td 173.37963 Tz (O ) Tj 1.468056 0 Td 37.268519 Tz (N ) Tj 31.428571 0 0 31.428571 0 466 Tm 23.418182 0 Td 106.060606 Tz (HO ) Tj 40 0 0 40 0 275 Tm 23.35 0 Td 72.222222 Tz (NH2 ) Tj 84.285714 0 0 84.285714 0 898 Tm 16.776271 0 Td 58.827684 Tz (Hos-os-s ) Tj 31.428571 0 0 31.428571 0 885 Tm 49.190909 0 Td 108.712121 Tz (HN ) Tj 2.863636 0 Td 95.454545 Tz (NO ) Tj 30 0 0 30 0 883 Tm 41.6 0 Td 80.555556 Tz (50 ) Tj 31.428571 0 0 31.428571 0 835 Tm 52.531818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 853 Tm 56.731818 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 810 Tm 54.345455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 760 Tm 50.622727 0 Td 106.060606 Tz (HN ) Tj 3.722727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 673 Tm 53.804545 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 630 Tm 46.581818 0 Td 106.060606 Tz (HO ) Tj 11.740909 0 Td 111.363636 Tz (NH ) Tj 3.022727 0 Td 106.060606 Tz (O ) Tj 62.142857 0 0 62.142857 0 575.692308 Tm 25.071264 0 Td 56.321839 Tz (O ) Tj 3.218391 0 Td 56.321839 Tz (O ) Tj 1.496552 0 Td 56.321839 Tz (\\ ) Tj 0.885057 0 Td 75.095785 Tz ({ ) Tj 130 0 0 130 0 509 Tm 14.823077 0 Td 40.865385 Tz (oK\)-No. ) Tj 51.428571 0 0 51.428571 0 409.604969 Tm 26.036111 0 Td 48.611111 Tz (11. ) Tj 0.991667 0 Td 72.916667 Tz (An ) Tj 1.030556 0 Td 46.450617 Tz (orally ) Tj 1.827778 0 Td 49.259259 Tz (digestable ) Tj 3.091667 0 Td 54.208754 Tz (composition ) Tj 3.713889 0 Td 51.131687 Tz (including ) Tj 2.877778 0 Td 45.37037 Tz (at ) Tj 0.7 0 Td 44.074074 Tz (least ) Tj 1.438889 0 Td 59.41358 Tz (one ) Tj 51.428571 0 0 51.428571 0 367.399021 Tm 25.297222 0 Td 50.05144 Tz (autotaxin ) Tj 2.955556 0 Td 46.450617 Tz (inhibitor ) Tj 2.702778 0 Td 64.00463 Tz (compound ) Tj 3.305556 0 Td 48.611111 Tz (selected ) Tj 2.547222 0 Td 58.333333 Tz (from ) Tj 1.633333 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 56.388889 Tz (group ) Tj 1.925 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 328.566013 Tm 25.316667 0 Td 44.907407 Tz (sisting ) Tj 2.197222 0 Td 55.092593 Tz (of ) Tj 0.855556 0 Td 46.990741 Tz (at ) Tj 0.836111 0 Td 44.722222 Tz (least ) Tj 1.652778 0 Td 57.253086 Tz (one ) Tj 1.341667 0 Td 63.599537 Tz (compound ) Tj 3.344444 0 Td 49.016204 Tz (selected ) Tj 2.625 0 Td 58.333333 Tz (from ) Tj 1.711111 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 289.387755 Tm 25.297222 0 Td 49.259259 Tz (consisting ) Tj 3.227778 0 Td 55.092593 Tz (of ) Tj 0.836111 0 Td 43.75 Tz (at ) Tj 0.777778 0 Td 44.074074 Tz (least ) Tj 1.594444 0 Td 57.253086 Tz (one ) Tj 1.302778 0 Td 53.030303 Tz (naphthalene ) Tj 3.733333 0 Td 48.611111 Tz (Sulfone, ) Tj 2.566667 0 Td 43.75 Tz (at ) Tj 0.797222 0 Td 44.722222 Tz (least ) Tj 1.575 0 Td 58.333333 Tz (one ) Tj 51.428571 0 0 51.428571 0 248.569067 Tm 25.297222 0 Td 50.925926 Tz (phenylsulfone, ) Tj 4.394444 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 56.17284 Tz (any ) Tj 1.166667 0 Td 52.256944 Tz (mixtures ) Tj 2.625 0 Td 46.585648 Tz (thereof, ) Tj 2.372222 0 Td 55.555556 Tz (wherein ) Tj 2.469444 0 Td 48.611111 Tz (said ) Tj 1.283333 0 Td 43.75 Tz (at ) Tj 0.641667 0 Td 44.722222 Tz (least ) Tj 51.428571 0 0 51.428571 0 209.057971 Tm 25.297222 0 Td 58.333333 Tz (one ) Tj 1.186111 0 Td 53.098291 Tz (phenylsulfone ) Tj 4.277778 0 Td 55.092593 Tz (meets ) Tj 1.808333 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 47.530864 Tz (structure ) Tj 2.683333 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 46.990741 Tz (at ) Tj 0.7 0 Td 44.074074 Tz (least ) Tj 1.458333 0 Td 58.333333 Tz (one ) Tj 1.166667 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 81.018519 Tz (C ) Tj 0.622222 0 Td 59.41358 Tz (and ) Tj 38.571429 0 0 38.571429 0 175 Tm 33.755556 0 Td 73.45679 Tz (D: ) Tj 30 0 0 30 0 259 Tm 41.633333 0 Td 75 Tz (65 ) Tj ET Q endstream endobj 210 0 obj << /Length 1 >> stream q endstream endobj 211 0 obj << /Length 7115 >> stream Q q 0.24 0 0 0.24 0 0 cm BT /F1 1 Tf 3 Tr 62.857143 0 0 62.857143 0 3023 Tm 17.325 0 Td 83.522727 Tz (US ) Tj 1.240909 0 Td 58.333333 Tz (8,343.934 ) Tj 3.388636 0 Td 74.242424 Tz (B2 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 14.602778 0 Td 76.157407 Tz (21 ) Tj 18.938889 0 Td 77.777778 Tz (22 ) Tj 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 40 0 0 40 0 2873 Tm 32.6 0 Td 62.5 Tz (D\) ) Tj 35 0 0 35 0 2755.682927 Tm 9.657143 0 Td 66.666667 Tz (C\) ) Tj 26.2 0 Td 61.904762 Tz (5 ) Tj 34.285714 0 0 34.285714 0 2674 Tm 21.204167 0 Td 68.055556 Tz (A ) Tj 31.428571 0 0 31.428571 0 2650.895604 Tm 12.313636 0 Td 127.272727 Tz (HO-S ) Tj 10.245455 0 Td 121.969697 Tz (N ) Tj 30.004545 0 Td 111.363636 Tz (O ) Tj 4.168182 0 Td 111.363636 Tz (OH ) Tj 57.142857 0 0 57.142857 0 2606.96875 Tm 18.235 0 Td 32.083333 Tz (| ) Tj 11.655 0 Td 61.25 Tz (O ) Tj 31.428571 0 0 31.428571 0 2588 Tm 14.827273 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2569 Tm 50.622727 0 Td 106.060606 Tz (HN ) Tj 3.722727 0 Td 111.363636 Tz (O ) Tj 100.714286 0 0 100.714286 0 2459.166667 Tm 8.886525 0 Td 172.104019 Tz (O ) Tj 7.903546 0 Td 33.096927 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2439 Tm 46.581818 0 Td 106.060606 Tz (HO ) Tj 11.740909 0 Td 111.363636 Tz (NH ) Tj 2.959091 0 Td 111.363636 Tz (O ) Tj 56 0 0 56 0 2390.707692 Tm 13.464286 0 Td 59.52381 Tz (HO ) Tj 14.357143 0 Td 62.5 Tz (O ) Tj 3.571429 0 Td 62.5 Tz (O ) Tj 1.660714 0 Td 62.5 Tz (\\ ) Tj 0.982143 0 Td 80.357143 Tz ({ ) Tj 143.928571 0 0 143.928571 0 2310.027855 Tm 5.857072 0 Td 44.003309 Tz (\( ) Tj 0.562779 0 Td 50.951199 Tz (\) ) Tj 2.278908 0 Td 13.895782 Tz (is ) Tj 4.682878 0 Td 36.621175 Tz (oK\)-No. ) Tj 40 0 0 40 0 2221 Tm 23.825 0 Td 72.222222 Tz (NH2 ) Tj 9.65 0 Td 62.5 Tz (12. ) Tj 1.55 0 Td 80.555556 Tz (The ) Tj 1.875 0 Td 77.777778 Tz (method ) Tj 3.225 0 Td 70.833333 Tz (of ) Tj 1.15 0 Td 68.333333 Tz (claim ) Tj 2.525 0 Td 68.75 Tz (11 ) Tj 1.325 0 Td 70.833333 Tz (wherein ) Tj 3.4 0 Td 62.5 Tz (said ) Tj 1.9 0 Td 58.333333 Tz (at ) Tj 1.1 0 Td 56.666667 Tz (least ) Tj 2.1 0 Td 75 Tz (one ) Tj 51.428571 0 0 51.428571 0 2177.286169 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 1.536111 0 Td 57.253086 Tz (one ) Tj 1.244444 0 Td 52.73569 Tz (naphthalene ) Tj 3.675 0 Td 47.800926 Tz (Sulfone. ) Tj 55.714286 0 0 55.714286 0 2132.888325 Tm 22.651282 0 Td 35.897436 Tz (o ) Tj 1.382051 0 Td 45.868946 Tz (13. ) Tj 0.951282 0 Td 59.82906 Tz (The ) Tj 1.220513 0 Td 50.582751 Tz (composition ) Tj 3.482051 0 Td 53.846154 Tz (of ) Tj 0.735897 0 Td 49.059829 Tz (claim ) Tj 1.669231 0 Td 53.846154 Tz (12 ) Tj 0.807692 0 Td 51.282051 Tz (wherein ) Tj 2.333333 0 Td 44.871795 Tz (said ) Tj 1.220513 0 Td 41.880342 Tz (at ) Tj 0.682051 0 Td 40.683761 Tz (least ) Tj 1.382051 0 Td 53.846154 Tz (one ) Tj 51.428571 0 0 51.428571 0 2093.861183 Tm 25.297222 0 Td 53.324916 Tz (naphthalene ) Tj 3.811111 0 Td 50.925926 Tz (sulfone ) Tj 2.430556 0 Td 55.740741 Tz (meets ) Tj 1.983333 0 Td 47.530864 Tz (the ) Tj 1.166667 0 Td 47.530864 Tz (structure ) Tj 2.819444 0 Td 59.953704 Tz (of ) Tj 0.875 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 44.722222 Tz (least ) Tj 1.613889 0 Td 59.41358 Tz (one ) Tj 1.341667 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 2055.931507 Tm 25.297222 0 Td 64.814815 Tz (Compounds ) Tj 3.675 0 Td 84.259259 Tz (A ) Tj 0.680556 0 Td 59.41358 Tz (and ) Tj 1.283333 0 Td 50.231481 Tz (B: ) Tj 40 0 0 40 0 1949 Tm 11.275 0 Td 64.583333 Tz (A\) ) Tj 31.428571 0 0 31.428571 0 1901 Tm 19.6 0 Td 111.363636 Tz (O ) Tj 70.714286 0 0 70.714286 0 1853.444444 Tm 7.113131 0 Td 40.06734 Tz (HO- ) Tj 1.244444 0 Td 35.353535 Tz (4. ) Tj 37.142857 0 0 37.142857 0 1809.045455 Tm 15.130769 0 Td 116.666667 Tz (M ) Tj 11.442308 0 Td 94.230769 Tz (O ) Tj 9.369231 0 Td 94.230769 Tz (C ) Tj 3.123077 0 Td 89.74359 Tz (H ) Tj 31.428571 0 0 31.428571 0 1780 Tm 17.468182 0 Td 111.363636 Tz (O ) Tj 45.181818 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1744 Tm 38.722727 0 Td 111.363636 Tz (O ) Tj 7.381818 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 1710.217172 Tm 29.559091 0 Td 121.969697 Tz (N ) Tj 25.804545 0 Td 106.060606 Tz (H ) Tj 5.154545 0 Td 164.393939 Tz (OESEO ) Tj 32.857143 0 0 32.857143 0 1643 Tm 19.204348 0 Td 157.246377 Tz (OESEO ) Tj 9.130435 0 Td 101.449275 Tz (H ) Tj 24.56087 0 Td 116.666667 Tz (N ) Tj 31.428571 0 0 31.428571 0 1609.522727 Tm 38.722727 0 Td 121.969697 Tz (N ) Tj 7.381818 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1573 Tm 22.209091 0 Td 111.363636 Tz (OH ) Tj 45.181818 0 Td 111.363636 Tz (O ) Tj 37.5 0 0 37.5 0 1539.05618 Tm 32.506667 0 Td 88.888889 Tz (H ) Tj 3.093333 0 Td 93.333333 Tz (C ) Tj 9.2 0 Td 93.333333 Tz (O ) Tj 11.12 0 Td 120 Tz (M ) Tj 31.428571 0 0 31.428571 0 1509 Tm 66.436364 0 Td 74.242424 Tz (S ) Tj 57.142857 0 0 57.142857 0 1476 Tm 36.1025 0 Td 75.833333 Tz (A ) Tj 0.7525 0 Td 76.805556 Tz (YoH ) Tj 75.714286 0 0 75.714286 0 1452 Tm 27.220755 0 Td 68.238994 Tz (/ ) Tj 40 0 0 40 0 1409 Tm 11.325 0 Td 58.333333 Tz (B\) ) Tj 31.428571 0 0 31.428571 0 1319 Tm 37.990909 0 Td 111.363636 Tz (O ) Tj 8.909091 0 Td 111.363636 Tz (O ) Tj 70.357143 0 0 70.357143 0 1271.61236 Tm 15.37868 0 Td 38.691483 Tz (HO- ) Tj 1.236548 0 Td 35.532995 Tz (4. ) Tj 4.519797 0 Td 45.00846 Tz (\\, ) Tj 0.867005 0 Td 48.166949 Tz (-OH ) Tj 49.285714 0 0 49.285714 0 1228 Tm 23.110145 0 Td 74.396135 Tz (/ ) Tj 7.872464 0 Td 77.777778 Tz (M ) Tj 77.857143 0 0 77.857143 0 1204 Tm 14.590826 0 Td 68.501529 Tz (/ ) Tj 4.93211 0 Td 44.954128 Tz (\\, ) Tj 31.428571 0 0 31.428571 0 1129 Tm 36.909091 0 Td 121.969697 Tz (N ) Tj 34.285714 0 0 34.285714 0 1059.355932 Tm 33.833333 0 Td 111.805556 Tz (N ) Tj 3.383333 0 Td 104.513889 Tz (OH ) Tj 3.383333 0 Td 84.259259 Tz (NH2 ) Tj 91.428571 0 0 91.428571 0 866 Tm 7.021875 0 Td 38.28125 Tz (pi ) Tj 32.857143 0 0 32.857143 0 828 Tm 17.469565 0 Td 156.231884 Tz (OESEO ) Tj 5.569565 0 Td 111.594203 Tz (N ) Tj 31.428571 0 0 31.428571 0 762 Tm 24.054545 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 628 Tm 24.054545 0 Td 111.363636 Tz (OH ) Tj 40 0 0 40 0 456 Tm 14.575 0 Td 72.222222 Tz (NH2 ) Tj 40 0 0 40 0 316 Tm 33.475 0 Td 62.5 Tz (14. ) Tj 1.55 0 Td 80.555556 Tz (The ) Tj 1.875 0 Td 77.777778 Tz (method ) Tj 3.225 0 Td 70.833333 Tz (of ) Tj 1.15 0 Td 68.333333 Tz (claim ) Tj 2.525 0 Td 68.75 Tz (11 ) Tj 1.325 0 Td 70.833333 Tz (wherein ) Tj 3.4 0 Td 62.5 Tz (said ) Tj 1.9 0 Td 58.333333 Tz (at ) Tj 1.1 0 Td 56.666667 Tz (least ) Tj 2.1 0 Td 75 Tz (one ) Tj 51.428571 0 0 51.428571 0 273.59383 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.402778 0 Td 40.509259 Tz (is ) Tj 0.836111 0 Td 43.75 Tz (at ) Tj 0.875 0 Td 44.722222 Tz (least ) Tj 1.652778 0 Td 58.333333 Tz (one ) Tj 1.4 0 Td 47.800926 Tz (said ) Tj 1.477778 0 Td 53.347578 Tz (phenylsulfone ) Tj 4.472222 0 Td 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