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(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 0 968.989899 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 0 926.050292 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 0 883.356718 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 0 841.277247 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 0 657.282667 Tm 6.358333 0 Td 53.347578 Tz (phophodiester ) Tj 4.394444 0 Td 58.333333 Tz (bonds ) Tj 2.041667 0 Td 59.953704 Tz (of ) Tj 0.952778 0 Td 61.574074 Tz (LPC, ) Tj 1.788889 0 Td 48.611111 Tz (as ) Tj 0.894444 0 Td 51.041667 Tz (well ) Tj 1.536111 0 Td 51.851852 Tz (as ) Tj 0.933333 0 Td 37.808642 Tz (its ) Tj 0.972222 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 51.851852 Tz (as ) Tj 0.933333 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 617.700885 Tm 6.358333 0 Td 53.596866 Tz (phospholipase ) Tj 4.336111 0 Td 63.194444 Tz (enzyme ) Tj 2.45 0 Td 50.555556 Tz (\(note ) Tj 1.730556 0 Td 57.407407 Tz (Formula ) Tj 2.625 0 Td 33.487654 Tz (I\). ) Tj 31.428571 0 0 31.428571 0 497 Tm 35.35 0 Td 74.242424 Tz (Formula ) Tj 3.372727 0 Td 53.030303 Tz (I ) Tj 31.428571 0 0 31.428571 0 438 Tm 19.25 0 Td 111.363636 Tz (O ) Tj 51.428571 0 0 51.428571 0 398 Tm 11.861111 0 Td 35.648148 Tz (| ) Tj 31.428571 0 0 31.428571 0 373 Tm 17.181818 0 Td 159.090909 Tz (O-P-O ) Tj 11.2 0 Td 111.363636 Tz (O ) Tj 3.563636 0 Td 169.69697 Tz (CH ) Tj 43.928571 0 0 43.928571 0 347.244821 Tm 7.421138 0 Td 202.98103 Tz (N1a- ) Tj 8.331707 0 Td 149.485095 Tz (n-1N1 ) Tj 7.64878 0 Td 45.528455 Tz (17133 ) Tj 2.481301 0 Td 75.880759 Tz (ATX ) Tj 59.047619 0 0 59.047619 0 299.675676 Tm 5.520968 0 Td 115.725806 Tz (1 ) Tj 1.083871 0 Td 79.032258 Tz (\\ ) Tj 3.641129 0 Td 59.274194 Tz (OH ) Tj 31.428571 0 0 31.428571 0 438 Tm 25.55 0 Td 106.060606 Tz (H ) Tj 31.428571 0 0 31.428571 0 277 Tm 30.163636 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 224 Tm 21.636364 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 91.428571 0 0 91.428571 0 2843 Tm 18.495313 0 Td 40.104167 Tz (9" ) Tj 65 0 0 65 0 2796.428571 Tm 21.892308 0 Td 86.752137 Tz (HO-P-O-N-N-O ) Tj 7.707692 0 Td 35.897436 Tz (C17H33 ) Tj 24.285714 0 0 24.285714 0 2785 Tm 84.741176 0 Td 58.333333 Tz (-- ) Tj 31.428571 0 0 31.428571 0 2752 Tm 48.045455 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 2718 Tm 59.372727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2666 Tm 53.772727 0 Td 93.686869 Tz (LPA ) Tj 31.428571 0 0 31.428571 0 2627 Tm 68.536364 0 Td 111.363636 Tz (OH ) Tj 75.714286 0 0 75.714286 0 2544 Tm 25.503774 0 Td 90.251572 Tz (1 ) Tj 0.871698 0 Td 66.037736 Tz (\\ ) Tj 31.428571 0 0 31.428571 0 2492 Tm 64.336364 0 Td 65.151515 Tz (choline ) Tj 51.428571 0 0 51.428571 0 2378.038926 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 2335.116129 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 2295.907455 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 2252.3 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 2211.626943 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 2168.54933 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 (\(Such ) Tj 1.75 0 Td 44.290123 Tz (as, ) Tj 1.011111 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 47.170782 Tz (instance, ) Tj 51.428571 0 0 51.428571 0 2127.713043 Tm 25.277778 0 Td 49.151235 Tz (breast ) Tj 1.983333 0 Td 54.012346 Tz (cancer ) Tj 2.138889 0 Td 41.666667 Tz (cells\), ) 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 2087.184178 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 2044.993412 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 2004.536618 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 1960.55122 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 1919.269368 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 1880.067416 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 1836.230179 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 1793.751269 Tm 25.297222 0 Td 44.722222 Tz (least ) Tj 1.613889 0 Td 49.537037 Tz (reduce, ) Tj 2.313889 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 61.574074 Tz (amount ) Tj 2.45 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 71.296296 Tz (LPA ) Tj 1.555556 0 Td 50.771605 Tz (within ) Tj 2.061111 0 Td 66.111111 Tz (human ) Tj 2.236111 0 Td 59.953704 Tz (body ) Tj 1.691667 0 Td 51.851852 Tz (holds ) Tj 51.428571 0 0 51.428571 0 1756.089987 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 1712 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 1671.622378 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 52.857143 0 0 52.857143 0 1633.80198 Tm 24.594595 0 Td 50 Tz (version ) Tj 2.289189 0 Td 55.18018 Tz (from ) Tj 1.532432 0 Td 71.471471 Tz (LPC ) Tj 1.456757 0 Td 44.144144 Tz (to ) Tj 0.756757 0 Td 58.333333 Tz (LPA; ) Tj 1.627027 0 Td 47.297297 Tz (the ) Tj 1.002703 0 Td 42.792793 Tz (ability ) Tj 1.986486 0 Td 44.144144 Tz (to ) Tj 0.718919 0 Td 46.509009 Tz (actually ) Tj 2.421622 0 Td 53.918919 Tz (accomplish ) Tj 51.428571 0 0 51.428571 0 1590.977778 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 1552.520315 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 1512.55092 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 51.428571 0 0 51.428571 0 1475.526882 Tm 25.297222 0 Td 45.664983 Tz (drastically ) Tj 3.227778 0 Td 52.932099 Tz (reduce ) Tj 2.061111 0 Td 48.611111 Tz (the ) Tj 0.991667 0 Td 45.37037 Tz (activity ) Tj 2.333333 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 53.148148 Tz (while ) Tj 1.75 0 Td 44.722222 Tz (also, ) Tj 1.477778 0 Td 55.092593 Tz (prefer ) Tj 51.428571 0 0 51.428571 0 1437.797297 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 1401 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 1356.265306 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 1318.714976 Tm 25.297222 0 Td 57.253086 Tz (any ) Tj 1.205556 0 Td 44.290123 Tz (efficacy, ) Tj 2.547222 0 Td 51.041667 Tz (and, ) Tj 1.419444 0 Td 61.574074 Tz (more ) Tj 1.633333 0 Td 48.881173 Tz (importantly, ) Tj 3.713889 0 Td 49.421296 Tz (Zinc ) Tj 1.361111 0 Td 45.833333 Tz (sulfate ) Tj 2.080556 0 Td 53.06713 Tz (presence ) Tj 2.722222 0 Td 44.290123 Tz (\(in ) Tj 51.428571 0 0 51.428571 0 1275.53125 Tm 25.316667 0 Td 52.10114 Tz (Submillimolar ) Tj 4.686111 0 Td 49.691358 Tz (concentrations\) ) Tj 5.133333 0 Td 52.932099 Tz (suggested ) Tj 3.461111 0 Td 58.333333 Tz (an ) Tj 1.341667 0 Td 47.314815 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 1236.384049 Tm 25.297222 0 Td 60.853909 Tz (mechanism ) Tj 3.538889 0 Td 50.771605 Tz (involving ) Tj 2.975 0 Td 46.843434 Tz (interaction ) Tj 3.325 0 Td 53.472222 Tz (with ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 60.493827 Tz (two ) Tj 1.341667 0 Td 48.070988 Tz (native ) Tj 1.944444 0 Td 48.070988 Tz (active ) Tj 51.428571 0 0 51.428571 0 1196.287129 Tm 25.316667 0 Td 41.319444 Tz (site ) Tj 1.225 0 Td 52.5 Tz (metal ) Tj 1.827778 0 Td 48.611111 Tz (ions ) Tj 1.419444 0 Td 45.775463 Tz (thereof. ) Tj 2.430556 0 Td 55.740741 Tz (Other ) Tj 1.866667 0 Td 46.8107 Tz (potential ) Tj 2.702778 0 Td 78.858025 Tz (ATX ) Tj 1.633333 0 Td 46.342593 Tz (inhibitors ) Tj 2.975 0 Td 57.523148 Tz (have ) Tj 51.428571 0 0 51.428571 0 1160.962515 Tm 25.297222 0 Td 52.256944 Tz (included ) Tj 2.761111 0 Td 48.611111 Tz (the ) Tj 1.088889 0 Td 52.256944 Tz (products ) Tj 2.741667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 56.837607 Tz (ATX-catalyzed ) Tj 4.627778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.266667 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 71.296296 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 1120.484076 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.4 0 Td 51.851852 Tz (sphingosyl ) Tj 3.480556 0 Td 53.376906 Tz (phosphorylcholine ) Tj 5.794444 0 Td 52.932099 Tz (\(SPC\), ) Tj 2.294444 0 Td 61.574074 Tz (LPA, ) Tj 1.827778 0 Td 58.333333 Tz (and ) Tj 1.419444 0 Td 51.041667 Tz (S1P. ) Tj 51.428571 0 0 51.428571 0 1080.334132 Tm 25.297222 0 Td 46.118234 Tz (respectively. ) Tj 3.791667 0 Td 46.990741 Tz (Inhibition ) Tj 2.955556 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 76.697531 Tz (ATX ) Tj 1.497222 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 70.216049 Tz (LPA ) Tj 1.419444 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 65.895062 Tz (S1P ) Tj 1.322222 0 Td 51.041667 Tz (suggests ) Tj 2.586111 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 1040.168894 Tm 25.297222 0 Td 53.240741 Tz (product ) Tj 2.430556 0 Td 55.497685 Tz (feedback ) Tj 2.858333 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 66.975309 Tz (may ) Tj 1.419444 0 Td 49.259259 Tz (contribute ) Tj 3.169444 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 48.287037 Tz (regulation ) Tj 3.130556 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 1000.835443 Tm 25.297222 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 45.37037 Tz (in ) Tj 0.875 0 Td 46.018519 Tz (vivo. ) Tj 1.730556 0 Td 50.555556 Tz (Previously ) Tj 3.344444 0 Td 50.231481 Tz (reported ) Tj 2.663889 0 Td 76.697531 Tz (ATX ) Tj 1.672222 0 Td 46.342593 Tz (inhibitors ) Tj 51.428571 0 0 51.428571 0 960.178266 Tm 25.316667 0 Td 50.555556 Tz (share ) Tj 1.711111 0 Td 48.148148 Tz (several ) Tj 2.255556 0 Td 70.216049 Tz (common ) Tj 2.741667 0 Td 45.694444 Tz (structural ) Tj 2.955556 0 Td 45.730453 Tz (features, ) Tj 2.702778 0 Td 50.411523 Tz (including ) Tj 2.936111 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 67.24537 Tz (phos ) Tj 51.428571 0 0 51.428571 0 925.443084 Tm 25.297222 0 Td 48.611111 Tz (phate, ) Tj 2.061111 0 Td 50.925926 Tz (thiophosphate, ) Tj 4.627778 0 Td 53.472222 Tz (or ) Tj 0.933333 0 Td 55.976431 Tz (phosphonate ) Tj 4.005556 0 Td 56.893004 Tz (headgroup ) Tj 3.402778 0 Td 51.041667 Tz (attached ) Tj 51.428571 0 0 51.428571 0 879.761905 Tm 25.297222 0 Td 46.990741 Tz (either ) Tj 1.866667 0 Td 53.472222 Tz (with ) Tj 1.516667 0 Td 53.472222 Tz (or ) Tj 0.836111 0 Td 53.240741 Tz (without ) Tj 2.45 0 Td 51.851852 Tz (a ) Tj 0.544444 0 Td 47.530864 Tz (linker ) Tj 1.905556 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 56.712963 Tz (an ) Tj 0.913889 0 Td 47.962963 Tz (alkyl ) Tj 1.652778 0 Td 49.151235 Tz (chain, ) Tj 2.002778 0 Td 58.333333 Tz (which ) Tj 1.963889 0 Td 58.333333 Tz (can ) Tj 51.428571 0 0 51.428571 0 841.566295 Tm 25.297222 0 Td 52.662037 Tz (vary ) Tj 1.458333 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 47.222222 Tz (overall ) Tj 2.158333 0 Td 50.231481 Tz (length ) Tj 2.002778 0 Td 58.333333 Tz (and ) Tj 1.244444 0 Td 55.092593 Tz (can ) Tj 1.166667 0 Td 58.333333 Tz (be ) Tj 0.855556 0 Td 47.530864 Tz (either ) Tj 1.866667 0 Td 48.611111 Tz (Saturated ) Tj 2.8 0 Td 53.472222 Tz (or ) Tj 0.777778 0 Td 56.481481 Tz (unsatur ) Tj 51.428571 0 0 51.428571 0 801.665463 Tm 25.297222 0 Td 44.722222 Tz (ated. ) Tj 1.594444 0 Td 56.30787 Tz (However, ) Tj 2.916667 0 Td 49.907407 Tz (these ) Tj 1.633333 0 Td 62.294239 Tz (compounds ) Tj 3.538889 0 Td 53.472222 Tz (both ) Tj 1.477778 0 Td 51.041667 Tz (lack ) Tj 1.380556 0 Td 46.843434 Tz (substantial ) Tj 3.266667 0 Td 55.092593 Tz (struc ) Tj 51.428571 0 0 51.428571 0 765.098039 Tm 25.277778 0 Td 44.074074 Tz (tural ) Tj 1.516667 0 Td 46.090535 Tz (diversity ) Tj 2.663889 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 38.888889 Tz (fail ) Tj 1.127778 0 Td 42.12963 Tz (to ) Tj 0.719444 0 Td 59.143519 Tz (meet ) Tj 1.575 0 Td 48.611111 Tz (Lipinskis ) Tj 3.091667 0 Td 50.411523 Tz (empirical ) Tj 2.916667 0 Td 46.018519 Tz (rules ) Tj 1.555556 0 Td 46.180556 Tz (that ) Tj 51.428571 0 0 51.428571 0 723.507463 Tm 25.297222 0 Td 48.881173 Tz (characterize ) Tj 3.733333 0 Td 73.45679 Tz (90% ) Tj 1.555556 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 46.990741 Tz (orally ) Tj 1.905556 0 Td 49.421296 Tz (bioavailable ) Tj 3.791667 0 Td 48.070988 Tz (drugs. ) Tj 2.041667 0 Td 35.648148 Tz (It ) Tj 0.641667 0 Td 38.888889 Tz (is ) Tj 0.680556 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 49.259259 Tz (great ) Tj 51.428571 0 0 51.428571 0 686.340206 Tm 25.297222 0 Td 55.092593 Tz (importance ) Tj 3.636111 0 Td 48.611111 Tz (to ) Tj 0.972222 0 Td 46.990741 Tz (identify ) Tj 2.683333 0 Td 51.851852 Tz (novel ) Tj 2.002778 0 Td 48.611111 Tz (non-lipid ) Tj 3.013889 0 Td 45.694444 Tz (structural ) Tj 3.130556 0 Td 48.148148 Tz (classes ) Tj 51.428571 0 0 51.428571 0 645.355152 Tm 25.297222 0 Td 53.240741 Tz (capable ) Tj 2.411111 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 46.666667 Tz (inhibiting ) Tj 2.975 0 Td 76.697531 Tz (ATX ) Tj 1.575 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 57.685185 Tz (which ) Tj 1.944444 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 46.990741 Tz (orally ) Tj 1.866667 0 Td 49.421296 Tz (bioavailable ) Tj 40 0 0 40 0 611 Tm 32.5 0 Td 60.416667 Tz (to ) Tj 0.95 0 Td 56.666667 Tz (treat ) Tj 1.925 0 Td 60.119048 Tz (certain ) Tj 2.75 0 Td 76.666667 Tz (tumor ) Tj 2.525 0 Td 57.8125 Tz (classes. ) Tj 51.428571 0 0 51.428571 0 566.564661 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 0 526.445798 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 0 484.722444 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 0 446.342355 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 51.428571 0 0 51.428571 0 406.429698 Tm 25.316667 0 Td 55.092593 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 61.574074 Tz (860 ) Tj 1.4 0 Td 59.62963 Tz (amino ) Tj 2.1 0 Td 49.907407 Tz (acids ) Tj 1.808333 0 Td 38.888889 Tz (is ) Tj 0.777778 0 Td 51.851852 Tz (divided ) Tj 2.488889 0 Td 45.37037 Tz (into ) Tj 1.438889 0 Td 47.685185 Tz (several ) Tj 51.428571 0 0 51.428571 0 370.093023 Tm 25.297222 0 Td 55.092593 Tz (domains, ) Tj 2.877778 0 Td 50.771605 Tz (including ) Tj 2.955556 0 Td 51.851852 Tz (a ) Tj 0.583333 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 0 334 Tm 32.525 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 2.05 0 Td 52.083333 Tz (is ) Tj 0.925 0 Td 70.833333 Tz (a ) Tj 0.725 0 Td 84.722222 Tz (member ) Tj 3.3 0 Td 77.083333 Tz (of ) Tj 1.075 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 65 Tz (nucleotide ) Tj 51.428571 0 0 51.428571 0 292.944186 Tm 25.297222 0 Td 52.637486 Tz (pyrophosphatase/phosphodiesterase ) Tj 10.558333 0 Td 60.925926 Tz (\(NPP\) ) Tj 1.983333 0 Td 47.685185 Tz (family, ) Tj 2.138889 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 0 252.681293 Tm 25.277778 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 0 211.487923 Tm 25.277778 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 2.508333 0 Td 54.503367 Tz (phosphatase ) Tj 3.85 0 Td 51.851852 Tz (Superfamily ) Tj 3.694444 0 Td 62.962963 Tz (members ) Tj 51.428571 0 0 51.428571 0 169.016688 Tm 25.277778 0 Td 57.523148 Tz (have ) Tj 1.672222 0 Td 57.523148 Tz (been ) Tj 1.730556 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 2.780556 0 Td 58.333333 Tz (These ) Tj 2.080556 0 Td 45.833333 Tz (crystal ) Tj 2.275 0 Td 46.990741 Tz (structures ) Tj ET Q endstream endobj 106 0 obj << /Length 1 >> stream q endstream endobj 107 0 obj << /Length 20996 >> 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 57.154882 Tz (8,268,891 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 52.142857 0 0 52.142857 0 2968.510638 Tm 14.652055 0 Td 73.515982 Tz (3 ) Tj 18.660274 0 Td 76.712329 Tz (4 ) Tj 40 0 0 40 0 2919.684481 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 58.333333 Tz (Sur- ) Tj 12.6 0 Td 66.666667 Tz (-continued ) Tj 51.428571 0 0 51.428571 0 2876.78961 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 2831.004926 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 49.206349 0 0 49.206349 0 2793.098976 Tm 6.665806 0 Td 54.193548 Tz (served ) Tj 2.072903 0 Td 48.774194 Tz (core. ) Tj 1.625806 0 Td 60.544355 Tz (Sequence ) Tj 3.007742 0 Td 63.931452 Tz (homology ) Tj 3.23129 0 Td 54.193548 Tz (of ) Tj 0.71129 0 Td 51.935484 Tz (the ) Tj 1.036452 0 Td 50.806452 Tz (alkaline ) Tj 2.52 0 Td 55.887097 Tz (phosphatases ) Tj 18.615484 0 Td 71.129032 Tz (O ) Tj 40 0 0 40 0 2755 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 4.925 0 Td 50 Tz (5 ) Tj 51.428571 0 0 51.428571 0 2710.692924 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 2668.540284 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 2623.88 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 49.61039 0 0 49.61039 0 2584.901163 Tm 6.571204 0 Td 48.899554 Tz (bacterial ) Tj 2.761518 0 Td 77.268761 Tz (NPP ) Tj 1.51178 0 Td 65.510471 Tz (enzyme ) Tj 2.479319 0 Td 56.271815 Tz (with ) Tj 1.491623 0 Td 76.148924 Tz (30% ) Tj 1.531937 0 Td 48.292976 Tz (identity ) Tj 2.459162 0 Td 47.033159 Tz (to ) Tj 0.725654 0 Td 51.512507 Tz (the ) Tj 1.02801 0 Td 79.508435 Tz (ATX ) Tj 1.572251 0 Td 47.406438 Tz (catalytic ) Tj 19.370942 0 Td 70.549738 Tz (O ) Tj 51.428571 0 0 51.428571 0 2540.757437 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 59.953704 Tz (of ) Tj 1.108333 0 Td 42.12963 Tz (10 ) Tj 57.792208 0 0 57.792208 0 2498.286498 Tm 5.640899 0 Td 45.181024 Tz (the ) Tj 0.917079 0 Td 69.213483 Tz (ATX ) Tj 1.401573 0 Td 40.374532 Tz (catalytic ) Tj 2.353258 0 Td 53.35206 Tz (domain ) Tj 2.076404 0 Td 40.374532 Tz (that ) Tj 1.124719 0 Td 59.600499 Tz (may ) Tj 1.228539 0 Td 49.026217 Tz (prove ) Tj 1.626517 0 Td 43.258427 Tz (useful ) Tj 1.730337 0 Td 38.932584 Tz (in ) Tj 0.622921 0 Td 41.2397 Tz (structure- ) Tj 14.431011 0 Td 132.659176 Tz (1s ) Tj 47.428571 0 0 47.428571 0 2462.851685 Tm 6.873494 0 Td 61.144578 Tz (based ) Tj 1.960843 0 Td 60.61747 Tz (drug ) Tj 1.60241 0 Td 53.212851 Tz (design. ) Tj 2.361446 0 Td 61.935241 Tz (Although ) Tj 3.099398 0 Td 63.253012 Tz (a ) Tj 0.527108 0 Td 49.835706 Tz (significant ) Tj 3.436747 0 Td 60.61747 Tz (improvement, ) Tj 4.533133 0 Td 60.61747 Tz (Such ) Tj 15.454819 0 Td 80.823293 Tz (N ) Tj 2.509036 0 Td 49.196787 Tz (S ) Tj 51.428571 0 0 51.428571 0 2417.915094 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 2374.184116 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 2333.287059 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 56.944444 Tz (domain- ) Tj 2.877778 0 Td 42.12963 Tz (15 ) Tj 51.428571 0 0 51.428571 0 2294.688645 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 2253.150617 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 2215.42654 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 48.571429 0 0 48.571429 0 2175.565287 Tm 6.711765 0 Td 55.392157 Tz (thereby ) Tj 2.552941 0 Td 51.041667 Tz (creating ) Tj 2.635294 0 Td 59.620098 Tz (problems ) Tj 3.067647 0 Td 49.754902 Tz (in ) Tj 0.782353 0 Td 48.897059 Tz (that ) Tj 1.358824 0 Td 48.039216 Tz (area. ) Tj 17.85 0 Td 49.509804 Tz (7839888 ) Tj 52.857143 0 0 52.857143 0 2132.405535 Tm 6.886486 0 Td 66.216216 Tz (As ) Tj 0.945946 0 Td 47.297297 Tz (such, ) Tj 1.57027 0 Td 47.927928 Tz (there ) Tj 1.551351 0 Td 44.144144 Tz (exists ) Tj 1.702703 0 Td 56.756757 Tz (a ) Tj 0.472973 0 Td 44.144144 Tz (definitive ) Tj 2.781081 0 Td 48.873874 Tz (lack ) Tj 1.286486 0 Td 45.720721 Tz (in ) Tj 0.681081 0 Td 51.151151 Tz (providing ) Tj 2.856757 0 Td 45.545546 Tz (effective ) Tj 2.875676 0 Td 45.720721 Tz (20 ) Tj 51.428571 0 0 51.428571 0 2090 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 2052.058537 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 2007.621266 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 51.428571 0 0 51.428571 0 1971.099617 Tm 6.338889 0 Td 46.450617 Tz (bioavailability ) Tj 4.627778 0 Td 52.662037 Tz (requirements ) Tj 4.238889 0 Td 46.450617 Tz (\(as ) Tj 1.302778 0 Td 57.928241 Tz (measured ) Tj 3.188889 0 Td 59.953704 Tz (by ) Tj 1.205556 0 Td 48.611111 Tz (Lipinski's ) Tj 31.428571 0 0 31.428571 0 2078 Tm 66.022727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2034 Tm 68.472727 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1959 Tm 55.3 0 Td 111.363636 Tz (O ) Tj 46.309524 0 0 46.309524 0 1925.175573 Tm 7.061183 0 Td 48.329049 Tz (rules\). ) Tj 2.245758 0 Td 80.976864 Tz (No ) Tj 1.187661 0 Td 61.182519 Tz (such ) Tj 1.727506 0 Td 62.082262 Tz (need ) Tj 1.662725 0 Td 59.982862 Tz (has ) Tj 1.29563 0 Td 62.982005 Tz (been ) Tj 1.770694 0 Td 65.981148 Tz (met ) Tj 1.403599 0 Td 47.506427 Tz (until ) Tj 1.684319 0 Td 61.182519 Tz (now. ) Tj 6.910026 0 Td 50.385604 Tz (25 ) Tj 6.132648 0 Td 75.578406 Tz (O ) Tj 8.896658 0 Td 75.578406 Tz (O ) Tj 59.84127 0 0 59.84127 0 1846.905681 Tm 6.634218 0 Td 67.95756 Tz (ADVANTAGES ) Tj 4.227851 0 Td 74.270557 Tz (AND ) Tj 1.52069 0 Td 57.374005 Tz (BRIEF ) Tj 1.938462 0 Td 60.766819 Tz (DESCRIPTION ) Tj 4.19443 0 Td 64.058355 Tz (OF ) Tj 7.018568 0 Td 64.058355 Tz (N ) Tj 1.487268 0 Td 242.307692 Tz (O ) Tj 2.941114 0 Td 242.307692 Tz (O ) Tj 2.590186 0 Td 64.058355 Tz (N ) Tj 38.571429 0 0 38.571429 0 1811 Tm 16.385185 0 Td 105.144033 Tz (THE ) Tj 2.177778 0 Td 98.422497 Tz (INVENTION ) Tj 31.428571 0 0 31.428571 0 1773 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 13.109091 0 Td 111.363636 Tz (O ) Tj 32.857143 0 0 32.857143 0 1637 Tm 42.63913 0 Td 106.521739 Tz (O ) Tj 57.142857 0 0 57.142857 0 1719.778338 Tm 6.3875 0 Td 35 Tz (It ) Tj 0.56 0 Td 37.916667 Tz (is ) Tj 0.6125 0 Td 45.208333 Tz (thus ) Tj 1.2425 0 Td 53.958333 Tz (an ) Tj 0.805 0 Td 48.935185 Tz (advantage ) Tj 2.8 0 Td 52.5 Tz (of ) Tj 0.7175 0 Td 44.722222 Tz (the ) Tj 0.9625 0 Td 45.416667 Tz (present ) Tj 2.0825 0 Td 45.046296 Tz (invention ) Tj 2.6075 0 Td 40.833333 Tz (to ) Tj 0.6475 0 Td 47.916667 Tz (provide ) Tj 2.5025 0 Td 30.625 Tz (so ) Tj 49.428571 0 0 49.428571 0 1680.45045 Tm 6.615607 0 Td 47.627649 Tz (reliable ) Tj 2.407514 0 Td 52.076643 Tz (autotaxin ) Tj 2.973988 0 Td 48.611111 Tz (inactivators ) Tj 3.66185 0 Td 49.454078 Tz (for ) Tj 0.991329 0 Td 52.825947 Tz (the ) Tj 1.072254 0 Td 57.803468 Tz (purpose ) Tj 2.589595 0 Td 57.321773 Tz (of ) Tj 0.748555 0 Td 55.635838 Tz (reducing ) Tj 2.812139 0 Td 51.701991 Tz (the ) Tj 2.549133 0 Td 67.43738 Tz (HO ) Tj 52.857143 0 0 52.857143 0 1638.12304 Tm 6.186486 0 Td 51.081081 Tz (conversion ) Tj 3.216216 0 Td 55.18018 Tz (of ) Tj 0.737838 0 Td 71.471471 Tz (LPC ) Tj 1.4 0 Td 47.297297 Tz (to ) Tj 0.737838 0 Td 69.369369 Tz (LPA ) Tj 1.4 0 Td 51.801802 Tz (through ) Tj 2.308108 0 Td 49.399399 Tz (the ) Tj 1.059459 0 Td 42.997543 Tz (utilization ) Tj 2.989189 0 Td 53.603604 Tz (of ) Tj 0.718919 0 Td 53.603604 Tz (a ) Tj 0.454054 0 Td 47.297297 Tz (readily ) Tj 49.206349 0 0 49.206349 0 1599.265349 Tm 6.645484 0 Td 50.430108 Tz (available ) Tj 2.824839 0 Td 62.096774 Tz (and ) Tj 1.199032 0 Td 49.677419 Tz (easily ) Tj 1.910323 0 Td 59.274194 Tz (produced ) Tj 2.987419 0 Td 66.471774 Tz (compound ) Tj 3.312581 0 Td 50.806452 Tz (\(or ) Tj 1.016129 0 Td 62.66129 Tz (compounds\) ) Tj 3.86129 0 Td 48.266129 Tz (that ) Tj 10.750645 0 Td 48.387097 Tz (5761473 ) Tj 51.428571 0 0 51.428571 0 1555.936842 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 57.142857 0 0 57.142857 0 1512.182969 Tm 5.7225 0 Td 46.990741 Tz (necessary ) Tj 2.7475 0 Td 41.5625 Tz (oral ) Tj 1.1725 0 Td 41.611111 Tz (bioavailability ) Tj 3.9725 0 Td 45.769231 Tz (requirements. ) Tj 3.745 0 Td 51.25 Tz (Another ) Tj 2.31 0 Td 49.583333 Tz (advan- ) Tj 2.24 0 Td 35 Tz (is ) Tj 51.428571 0 0 51.428571 0 1473.46875 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 76 0 0 76 0 1428.540582 Tm 4.302632 0 Td 36.184211 Tz (cancer ) Tj 1.394737 0 Td 34.868421 Tz (prevention ) Tj 2.223684 0 Td 34.60039 Tz (treatment ) Tj 1.986842 0 Td 35.087719 Tz (regimens. ) Tj 17.513158 0 Td 239.035088 Tz (O ) Tj 31.428571 0 0 31.428571 0 1430 Tm 48.681818 0 Td 111.363636 Tz (O ) Tj 14.190909 0 Td 121.969697 Tz (N ) Tj 48.730159 0 0 48.730159 0 1391.297199 Tm 7.490228 0 Td 55.008143 Tz (Accordingly, ) Tj 4.309446 0 Td 47.027687 Tz (this ) Tj 1.518567 0 Td 52.062975 Tz (invention ) Tj 3.180782 0 Td 60.630737 Tz (encompasses ) Tj 4.391531 0 Td 58.143322 Tz (a ) Tj 0.738762 0 Td 62.703583 Tz (method ) Tj 2.62671 0 Td 51.302932 Tz (for ) Tj 12.025407 0 Td 71.824104 Tz (O ) Tj 4.801954 0 Td 82.084691 Tz (NN ) Tj 49.428571 0 0 49.428571 0 1349.50237 Tm 6.595376 0 Td 48.8921 Tz (treating ) Tj 2.589595 0 Td 55.448512 Tz (cancerous ) Tj 3.236994 0 Td 58.445729 Tz (tumors ) Tj 2.32659 0 Td 55.876686 Tz (through ) Tj 2.609827 0 Td 51.701991 Tz (the ) Tj 1.153179 0 Td 50.952687 Tz (ingestion ) Tj 2.99422 0 Td 62.379576 Tz (by ) Tj 1.011561 0 Td 53.949904 Tz (a ) Tj 0.566474 0 Td 47.768144 Tz (target ) Tj 6.49422 0 Td 67.43738 Tz (HN ) Tj 54.571429 0 0 54.571429 0 1303.037778 Tm 5.973822 0 Td 45.375218 Tz (patient ) Tj 1.997382 0 Td 46.116928 Tz (exhibiting ) Tj 2.858639 0 Td 48.86562 Tz (a ) Tj 0.421466 0 Td 50.901687 Tz (cancerous ) Tj 2.840314 0 Td 53.955788 Tz (tumorofat ) Tj 3.005236 0 Td 42.757417 Tz (least ) Tj 1.39267 0 Td 53.955788 Tz (one ) Tj 1.062827 0 Td 60.700262 Tz (compound ) Tj 3.335079 0 Td 45.811518 Tz (a ) Tj 9.602094 0 Td 70.244328 Tz (N ) Tj 31.428571 0 0 31.428571 0 1214 Tm 56.254545 0 Td 111.363636 Tz (O ) Tj 51.428571 0 0 51.428571 0 1264.326034 Tm 6.377778 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 57.523148 Tz (from ) Tj 1.555556 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 56.388889 Tz (group ) Tj 1.866667 0 Td 49.259259 Tz (consisting ) Tj 3.111111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 43.75 Tz (at ) Tj 0.680556 0 Td 44.722222 Tz (least ) Tj 1.477778 0 Td 58.333333 Tz (one ) Tj 1.205556 0 Td 47.530864 Tz (thiourea, ) Tj 2.722222 0 Td 45.37037 Tz (at ) Tj 51.428571 0 0 51.428571 0 1222.837093 Tm 6.358333 0 Td 44.722222 Tz (least ) Tj 1.613889 0 Td 57.253086 Tz (one ) Tj 1.263889 0 Td 50.951646 Tz (diphenyldiazerene, ) Tj 5.736111 0 Td 46.990741 Tz (at ) Tj 0.797222 0 Td 44.722222 Tz (least ) Tj 1.594444 0 Td 58.333333 Tz (one ) Tj 1.283333 0 Td 51.851852 Tz (Xanthene, ) Tj 3.072222 0 Td 45.37037 Tz (at ) Tj 0.777778 0 Td 44.722222 Tz (least ) Tj 49.428571 0 0 49.428571 0 1181.783883 Tm 6.615607 0 Td 61.817598 Tz (one ) Tj 1.416185 0 Td 48.8921 Tz (isoindole, ) Tj 3.216763 0 Td 61.817598 Tz (and ) Tj 1.395954 0 Td 59.569685 Tz (any ) Tj 1.416185 0 Td 53.949904 Tz (mixtures ) Tj 2.872832 0 Td 48.470617 Tz (thereof. ) Tj 2.67052 0 Td 50.578035 Tz (In ) Tj 0.890173 0 Td 46.593099 Tz (particular, ) Tj 3.378613 0 Td 51.701991 Tz (the ) Tj 2.589595 0 Td 67.43738 Tz (HO ) Tj 51.428571 0 0 51.428571 0 1140.971014 Tm 6.358333 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 49.691358 Tz (are ) Tj 1.069444 0 Td 48.611111 Tz (selected ) Tj 2.488889 0 Td 58.333333 Tz (from ) Tj 1.555556 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 57.037037 Tz (group ) Tj 1.905556 0 Td 48.935185 Tz (consisting ) Tj 3.091667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 44.722222 Tz (least ) Tj 44.52381 0 0 44.52381 0 1098.976608 Tm 7.344385 0 Td 68.627451 Tz (one ) Tj 1.392513 0 Td 69.251337 Tz (of ) Tj 0.920856 0 Td 58.645276 Tz (the ) Tj 1.257754 0 Td 57.272727 Tz (following: ) Tj 17.091979 0 Td 54.278075 Tz (45 ) Tj 2.942246 0 Td 78.609626 Tz (O ) Tj 31.428571 0 0 31.428571 0 1069 Tm 54.027273 0 Td 76.515152 Tz (5564949 ) Tj 31.428571 0 0 31.428571 0 987 Tm 37.831818 0 Td 111.363636 Tz (C ) Tj 28.285714 0 0 28.285714 0 959.338583 Tm 47.515152 0 Td 253.367003 Tz (o ) Tj 4.843434 0 Td 123.737374 Tz (O ) Tj 1.909091 0 Td 123.737374 Tz (O ) Tj 7.141414 0 Td 123.737374 Tz (O ) Tj 7.176768 0 Td 123.737374 Tz (O ) Tj 31.428571 0 0 31.428571 0 915 Tm 41.522727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 894.5 Tm 31.5 0 Td 106.060606 Tz (H ) Tj 32.009091 0 Td 106.060606 Tz (H ) Tj 47.142857 0 0 47.142857 0 875.184314 Tm 20.936364 0 Td 81.313131 Tz (N ) Tj 5.536364 0 Td 53.030303 Tz (so ) Tj 1.463636 0 Td 106.060606 Tz (V ) Tj 1.442424 0 Td 95.454545 Tz (/ ) Tj 2.015152 0 Td 86.026936 Tz (N-N ) Tj 9.842424 0 Td 84.848485 Tz (N-N ) Tj 48.571429 0 0 48.571429 0 842.453608 Tm 16.017647 0 Td 58.333333 Tz (/ ) Tj 1.873529 0 Td 58.333333 Tz (\\ ) Tj 12.641176 0 Td 68.627451 Tz (H ) Tj 12.373529 0 Td 89.215686 Tz (/ ) Tj 1.379412 0 Td 58.333333 Tz (\\ ) Tj 62.380952 0 0 62.380952 0 794.033113 Tm 10.772519 0 Td 93.51145 Tz (X-N ) Tj 3.462595 0 Td 61.450382 Tz (N ) Tj 20.535115 0 Td 61.450382 Tz (N ) Tj 54.642857 0 0 54.642857 0 779.790795 Tm 10.467974 0 Td 94.553377 Tz (N ) Tj 1.738562 0 Td 100.653595 Tz (/ ) Tj 1.775163 0 Td 91.503268 Tz (V ) Tj 1.921569 0 Td 70.152505 Tz (/ ) Tj 12.188235 0 Td 64.052288 Tz (O ) Tj 7.411765 0 Td 64.052288 Tz (O ) Tj 0.988235 0 Td 64.052288 Tz (O ) Tj 1.830065 0 Td 179.956427 Tz (V ) Tj 31.428571 0 0 31.428571 0 757.744526 Tm 31.531818 0 Td 74.242424 Tz (S ) Tj 6.3 0 Td 111.363636 Tz (C ) Tj 16.545455 0 Td 77.272727 Tz (5538444 ) Tj 30 0 0 30 0 675 Tm 41.6 0 Td 77.777778 Tz (55 ) Tj 31.428571 0 0 31.428571 0 628 Tm 68.281818 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 558.409836 Tm 23.036364 0 Td 76.515152 Tz (7905958 ) Tj 35.668182 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 514.570093 Tm 13.586364 0 Td 111.363636 Tz (OH ) Tj 21.445455 0 Td 111.363636 Tz (O ) Tj 18.2 0 Td 111.363636 Tz (O ) Tj 8.654545 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 488.463415 Tm 24.309091 0 Td 111.363636 Tz (O ) Tj 37.672727 0 Td 106.060606 Tz (H ) Tj 34.857143 0 0 34.857143 0 468.894737 Tm 10.069672 0 Td 100.409836 Tz (O ) Tj 5.967213 0 Td 100.409836 Tz (O ) Tj 11.790984 0 Td 100.409836 Tz (O ) Tj 5.967213 0 Td 102.800546 Tz (OH ) Tj 2.065574 0 Td 64.54918 Tz (60 ) Tj 132.142857 0 0 132.142857 0 325.624339 Tm 4.767568 0 Td 149.249249 Tz (oo: ) Tj 7.930811 0 Td 29.009009 Tz (N ) Tj 31.428571 0 0 31.428571 0 364 Tm 42.190909 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 295.983871 Tm 10.563636 0 Td 106.060606 Tz (HO ) Tj 7.222727 0 Td 111.363636 Tz (O ) Tj 13.077273 0 Td 111.363636 Tz (O ) Tj 6.618182 0 Td 111.363636 Tz (O ) Tj 15.75 0 Td 111.363636 Tz (O ) Tj 31.071429 0 0 31.071429 0 256.605505 Tm 13.742529 0 Td 112.643678 Tz (O ) Tj 21.08046 0 Td 107.279693 Tz (HO ) Tj 5.374713 0 Td 72.413793 Tz (65 ) Tj 4.956322 0 Td 112.643678 Tz (O ) Tj 31.428571 0 0 31.428571 0 226.502488 Tm 23.418182 0 Td 76.515152 Tz (5186522 ) Tj 30.609091 0 Td 75.757576 Tz (5711925 ) Tj 1.428571 0 0 1.428571 0 897 Tm 231 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 108 0 obj << /Length 1 >> stream q endstream endobj 109 0 obj << /Length 46038 >> 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 57.154882 Tz (8,268,891 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 51.428571 0 0 51.428571 0 2968 Tm 14.875 0 Td 74.537037 Tz (5 ) Tj 40 0 0 40 0 2913 Tm 17.475 0 Td 67.083333 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2887 Tm 12.377273 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2787 Tm 21.572727 0 Td 95.454545 Tz (O ) Tj 55.357143 0 0 55.357143 0 2702.468599 Tm 11.651613 0 Td 221.290323 Tz (1- ) Tj 2.727742 0 Td 42.150538 Tz (S ) Tj 2.023226 0 Td 69.247312 Tz (N ) Tj 2.095484 0 Td 69.247312 Tz (N ) Tj 62.380952 0 0 62.380952 0 2661.813793 Tm 9.922901 0 Td 61.450382 Tz (N ) Tj 3.158015 0 Td 240.458015 Tz (Y ) Tj 2.677099 0 Td 85.496183 Tz (2 ) Tj 31.428571 0 0 31.428571 0 2665 Tm 19.790909 0 Td 90.151515 Tz (H ) Tj 40 0 0 40 0 2610.111111 Tm 21.25 0 Td 95.833333 Tz (N ) Tj 3.325 0 Td 204.166667 Tz (N ) Tj 83.571429 0 0 83.571429 0 2526.865672 Tm 9.584615 0 Td 91.737892 Tz (r ) Tj 1.280342 0 Td 41.880342 Tz (O ) Tj 31.428571 0 0 31.428571 0 2483 Tm 23.036364 0 Td 66.287879 Tz (79.21385 ) Tj 31.428571 0 0 31.428571 0 2444 Tm 12.313636 0 Td 111.363636 Tz (OH ) Tj 13.490909 0 Td 111.363636 Tz (O ) Tj 220.47619 0 0 220.47619 0 2270.702479 Tm 1.578402 0 Td 29.481641 Tz (- ) Tj 0.42635 0 Td 75.593952 Tz (C ) Tj 1.011447 0 Td 77.861771 Tz (O ) Tj 31.428571 0 0 31.428571 0 2260 Tm 19.059091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2008 Tm 23.036364 0 Td 77.272727 Tz (5210574 ) Tj 51.428571 0 0 51.428571 0 1894.714994 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 90.740741 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1859.269377 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 (50% ) Tj 1.575 0 Td 53.472222 Tz (or ) Tj 51.428571 0 0 51.428571 0 1818 Tm 6.358333 0 Td 61.574074 Tz (more ) Tj 1.652778 0 Td 46.990741 Tz (at ) Tj 0.719444 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 50.605413 Tz (concentration ) Tj 4.122222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 53.796296 Tz (about ) Tj 1.886111 0 Td 55.092593 Tz (10 ) Tj 0.855556 0 Td 62.654321 Tz (uM. ) Tj 1.322222 0 Td 59.953704 Tz (Such ) Tj 1.633333 0 Td 51.851852 Tz (a ) Tj 0.525 0 Td 49.691358 Tz (reduction ) Tj 2.897222 0 Td 50.231481 Tz (in ) Tj 51.428571 0 0 51.428571 0 1783.613527 Tm 6.358333 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.05144 Tz (autotaxin ) Tj 2.877778 0 Td 38.888889 Tz (is ) Tj 0.641667 0 Td 47.530864 Tz (basically ) Tj 2.741667 0 Td 46.990741 Tz (in ) Tj 0.719444 0 Td 53.796296 Tz (terms ) Tj 1.808333 0 Td 55.092593 Tz (of ) Tj 0.719444 0 Td 47.170782 Tz (potential ) Tj 2.741667 0 Td 59.41358 Tz (conver ) Tj 51.428571 0 0 51.428571 0 1745.875622 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 58.873457 Tz (modifi ) Tj 51.428571 0 0 51.428571 0 1709.191411 Tm 6.358333 0 Td 49.074074 Tz (cations ) Tj 2.275 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 52.314815 Tz (prevent ) Tj 2.352778 0 Td 56.17284 Tz (placement ) Tj 3.188889 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 72.376543 Tz (LPC ) Tj 1.497222 0 Td 64.00463 Tz (compound ) Tj 3.286111 0 Td 46.180556 Tz (into ) Tj 1.322222 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1669.615509 Tm 6.358333 0 Td 48.070988 Tz (active ) Tj 1.905556 0 Td 42.12963 Tz (site ) Tj 1.186111 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 53.877315 Tz (modified ) Tj 2.761111 0 Td 49.691358 Tz (autotaxin ) Tj 2.877778 0 Td 57.87037 Tz (enzyme. ) Tj 38.571429 0 0 38.571429 0 1598 Tm 9.92963 0 Td 97.762346 Tz (DETAILED ) Tj 4.977778 0 Td 94.276094 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 98.902606 Tz (INVENTION ) Tj 38.571429 0 0 38.571429 0 1559 Tm 12.522222 0 Td 116.666667 Tz (AND ) Tj 2.385185 0 Td 101.303155 Tz (PREFERRED ) Tj 5.755556 0 Td 106.453423 Tz (EMBODIMENTS ) Tj 51.428571 0 0 51.428571 0 1474.744304 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.380556 0 Td 51.602564 Tz (determination ) Tj 4.258333 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 53.472222 Tz (proper ) Tj 2.119444 0 Td 77.777778 Tz (ATX ) Tj 1.672222 0 Td 46.666667 Tz (inhibition ) Tj 3.072222 0 Td 61.934156 Tz (compounds ) Tj 51.428571 0 0 51.428571 0 1433.874847 Tm 6.338889 0 Td 62.654321 Tz (was ) Tj 1.341667 0 Td 55.740741 Tz (based ) Tj 1.886111 0 Td 59.143519 Tz (upon ) Tj 1.633333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 46.254209 Tz (realization ) Tj 3.286111 0 Td 56.712963 Tz (of ) Tj 0.816667 0 Td 46.296296 Tz (certain ) Tj 2.158333 0 Td 45.694444 Tz (structural ) Tj 2.955556 0 Td 54.62963 Tz (require ) Tj 51.428571 0 0 51.428571 0 1396.979899 Tm 6.358333 0 Td 57.685185 Tz (ments ) Tj 1.983333 0 Td 48.611111 Tz (for ) Tj 1.088889 0 Td 54.012346 Tz (proper ) Tj 2.197222 0 Td 44.722222 Tz (reactivity ) Tj 2.955556 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 64.00463 Tz (compound ) Tj 3.344444 0 Td 37.962963 Tz (itself. ) Tj 51.428571 0 0 51.428571 0 1355.947368 Tm 6.377778 0 Td 52.572016 Tz (Extensive ) Tj 3.188889 0 Td 51.851852 Tz (review ) Tj 2.236111 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 49.826389 Tz (possible ) Tj 2.722222 0 Td 61.574074 Tz (compounds ) Tj 3.694444 0 Td 61.574074 Tz (was ) Tj 1.438889 0 Td 54.444444 Tz (undertaken ) Tj 51.428571 0 0 51.428571 0 1319.346784 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.663889 0 Td 57.118056 Tz (computer ) Tj 3.091667 0 Td 57.118056 Tz (modeling ) Tj 3.072222 0 Td 58.333333 Tz (of ) Tj 0.991667 0 Td 47.170782 Tz (similarly ) Tj 2.916667 0 Td 48.611111 Tz (structured ) Tj 3.247222 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1275.865337 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.313889 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 51.203704 Tz (types ) Tj 1.769444 0 Td 53.796296 Tz (noted ) Tj 1.808333 0 Td 57.685185 Tz (above ) Tj 1.944444 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 50.411523 Tz (exhibited ) Tj 2.897222 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 53.472222 Tz (inhibi ) Tj 51.428571 0 0 51.428571 0 1239.136253 Tm 6.338889 0 Td 44.074074 Tz (tion, ) Tj 1.477778 0 Td 50.771605 Tz (but ) Tj 1.069444 0 Td 50.771605 Tz (did ) Tj 1.05 0 Td 50.771605 Tz (not ) Tj 1.05 0 Td 51.851852 Tz (pass ) Tj 1.4 0 Td 46.180556 Tz (oral ) Tj 1.263889 0 Td 46.234568 Tz (bioavailability ) Tj 4.316667 0 Td 42.12963 Tz (test ) Tj 1.108333 0 Td 47.638889 Tz (protocols. ) Tj 3.072222 0 Td 37.268519 Tz (It ) Tj 0.583333 0 Td 60.493827 Tz (was ) Tj 51.428571 0 0 51.428571 0 1195.740214 Tm 6.358333 0 Td 52.146465 Tz (determined, ) Tj 3.597222 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 47.170782 Tz (instance, ) Tj 2.683333 0 Td 46.180556 Tz (that ) Tj 1.263889 0 Td 46.296296 Tz (certain ) Tj 2.1 0 Td 50.555556 Tz (types ) Tj 1.672222 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 58.333333 Tz (backbone ) Tj 2.916667 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1159.352657 Tm 6.358333 0 Td 58.333333 Tz (pounds ) Tj 2.275 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 44.722222 Tz (effective, ) Tj 2.838889 0 Td 47.314815 Tz (generally, ) Tj 2.975 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.231481 Tz (theory ) Tj 1.983333 0 Td 48.611111 Tz (for ) Tj 0.952778 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 56.712963 Tz (inhi ) Tj 51.428571 0 0 51.428571 0 1118.78392 Tm 6.338889 0 Td 44.444444 Tz (bition. ) Tj 2.197222 0 Td 57.118056 Tz (However, ) Tj 3.013889 0 Td 49.691358 Tz (closer ) Tj 2.022222 0 Td 48.206019 Tz (scrutiny ) Tj 2.625 0 Td 61.574074 Tz (was ) Tj 1.419444 0 Td 56.17284 Tz (needed ) Tj 2.294444 0 Td 46.990741 Tz (to ) Tj 0.855556 0 Td 46.548822 Tz (effectively ) Tj 51.428571 0 0 51.428571 0 1082.159269 Tm 6.358333 0 Td 53.703704 Tz (analyze ) Tj 2.411111 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 48.070988 Tz (actual ) Tj 1.925 0 Td 47.314815 Tz (capability ) Tj 3.052778 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 55.092593 Tz (each ) Tj 1.497222 0 Td 53.472222 Tz (type ) Tj 1.477778 0 Td 55.092593 Tz (of ) Tj 0.758333 0 Td 59.773663 Tz (compound. ) Tj 51.428571 0 0 51.428571 0 1038.182519 Tm 7.116667 0 Td 46.990741 Tz (In ) Tj 0.719444 0 Td 50.231481 Tz (essence, ) Tj 2.605556 0 Td 34.027778 Tz (it ) Tj 0.563889 0 Td 61.574074 Tz (was ) Tj 1.283333 0 Td 55.092593 Tz (determined ) Tj 3.441667 0 Td 53.240741 Tz (through ) Tj 2.411111 0 Td 55.092593 Tz (a ) Tj 0.544444 0 Td 58.981481 Tz (model ) Tj 1.944444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1000.728443 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.780556 0 Td 56.018519 Tz (domain, ) Tj 2.722222 0 Td 48.611111 Tz (residues ) Tj 2.761111 0 Td 55.555556 Tz (162-539 ) Tj 2.683333 0 Td 57.523148 Tz (from ) Tj 1.730556 0 Td 47.530864 Tz (the ) Tj 1.186111 0 Td 56.30787 Tz (sequence ) Tj 2.994444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 961.226572 Tm 6.338889 0 Td 66.759259 Tz (human ) Tj 2.1 0 Td 65.625 Tz (ATX, ) Tj 1.711111 0 Td 54.73251 Tz (developed ) Tj 3.072222 0 Td 58.333333 Tz (by ) Tj 0.816667 0 Td 61.574074 Tz (homology ) Tj 3.091667 0 Td 43.75 Tz (to ) Tj 0.661111 0 Td 64.814815 Tz (Xac ) Tj 1.302778 0 Td 58.333333 Tz (NPP, ) Tj 1.555556 0 Td 45.37037 Tz (that ) Tj 1.186111 0 Td 48.148148 Tz (certain ) Tj 51.428571 0 0 51.428571 0 921.866104 Tm 6.338889 0 Td 49.907407 Tz (basic ) Tj 1.672222 0 Td 49.537037 Tz (configurations ) Tj 4.316667 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 75.617284 Tz (ATX ) Tj 1.555556 0 Td 46.018519 Tz (inhibitors ) Tj 2.955556 0 Td 58.333333 Tz (were ) Tj 1.594444 0 Td 58.333333 Tz (most ) Tj 1.575 0 Td 44.830247 Tz (likely ) Tj 1.808333 0 Td 68.055556 Tz (nec ) Tj 51.428571 0 0 51.428571 0 880.014085 Tm 6.358333 0 Td 45.833333 Tz (essary. ) Tj 2.138889 0 Td 54.552469 Tz (Within ) Tj 2.177778 0 Td 42.12963 Tz (this ) Tj 1.244444 0 Td 54.012346 Tz (model, ) Tj 2.138889 0 Td 35.648148 Tz (it ) Tj 0.602778 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 53.148148 Tz (noted ) Tj 1.788889 0 Td 45.37037 Tz (that ) Tj 1.263889 0 Td 38.888889 Tz (all ) Tj 0.875 0 Td 51.851852 Tz (but ) Tj 1.127778 0 Td 58.333333 Tz (4 ) Tj 0.563889 0 Td 59.953704 Tz (\(1%\) ) Tj 1.613889 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 845.368047 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 60.493827 Tz (317 ) Tj 1.263889 0 Td 51.262626 Tz (non-proline ) Tj 3.519444 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 52.441077 Tz (non-glycine ) Tj 3.597222 0 Td 49.016204 Tz (residues ) Tj 2.527778 0 Td 57.253086 Tz (occupy ) Tj 2.216667 0 Td 50.462963 Tz (regions ) Tj 51.428571 0 0 51.428571 0 803.843787 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.758333 0 Td 60.493827 Tz (Ramachandran ) Tj 4.530556 0 Td 53.796296 Tz (space ) Tj 1.75 0 Td 50.968013 Tz (categorized ) Tj 3.5 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 51.851852 Tz (core ) Tj 1.419444 0 Td 54.012346 Tz (secondary ) Tj 3.091667 0 Td 54.444444 Tz (struc ) Tj 51.428571 0 0 51.428571 0 762.121887 Tm 6.338889 0 Td 47.314815 Tz (tures ) Tj 1.808333 0 Td 54.282407 Tz (\(232 ) Tj 1.691667 0 Td 46.8107 Tz (residues, ) Tj 2.897222 0 Td 57.685185 Tz (73%\), ) Tj 2.080556 0 Td 54.62963 Tz (allowed ) Tj 2.683333 0 Td 49.537037 Tz (regions ) Tj 2.430556 0 Td 54.012346 Tz (\(75 ) Tj 1.361111 0 Td 46.450617 Tz (residues, ) Tj 51.428571 0 0 51.428571 0 723.663391 Tm 6.358333 0 Td 66.435185 Tz (24%\) ) Tj 1.769444 0 Td 53.472222 Tz (or ) Tj 0.816667 0 Td 52.824074 Tz (generously ) Tj 3.363889 0 Td 55.092593 Tz (allowed ) Tj 2.527778 0 Td 50 Tz (regions ) Tj 2.313889 0 Td 48.611111 Tz (\(6 ) Tj 0.816667 0 Td 46.8107 Tz (residues, ) Tj 2.741667 0 Td 56.712963 Tz (2%\). ) Tj 1.575 0 Td 51.203704 Tz (\(This ) Tj 51.428571 0 0 51.428571 0 684.220452 Tm 6.358333 0 Td 60.277778 Tz (model ) Tj 2.138889 0 Td 52.662037 Tz (was, ) Tj 1.575 0 Td 48.070988 Tz (again, ) Tj 2.061111 0 Td 55.092593 Tz (used ) Tj 1.613889 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 55.555556 Tz (docking ) Tj 2.625 0 Td 47.685185 Tz (studies ) Tj 2.313889 0 Td 52.662037 Tz (with ) Tj 1.575 0 Td 59.41358 Tz (two ) Tj 1.4 0 Td 72.376543 Tz (LPC ) Tj 51.428571 0 0 51.428571 0 645.817509 Tm 6.377778 0 Td 46.990741 Tz (species, ) Tj 2.508333 0 Td 51.851852 Tz (12:0 ) Tj 1.380556 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 47.314815 Tz (14:0, ) Tj 1.594444 0 Td 62.222222 Tz (shown ) Tj 2.041667 0 Td 50.87963 Tz (previously ) Tj 3.266667 0 Td 43.75 Tz (to ) Tj 0.7 0 Td 59.953704 Tz (be ) Tj 0.875 0 Td 52.777778 Tz (optimal ) Tj 2.372222 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 605.291215 Tm 6.377778 0 Td 45.640432 Tz (substrates.\) ) Tj 3.461111 0 Td 51.851852 Tz (Unrestrained ) Tj 3.927778 0 Td 56.481481 Tz (docking ) Tj 2.527778 0 Td 47.685185 Tz (studies ) Tj 2.197222 0 Td 45.910494 Tz (failed ) Tj 1.847222 0 Td 43.75 Tz (to ) Tj 0.719444 0 Td 46.990741 Tz (identify ) Tj 2.45 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 566.524941 Tm 6.358333 0 Td 55.902778 Tz (pose ) Tj 1.477778 0 Td 51.388889 Tz (placing ) Tj 2.294444 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 56.271044 Tz (phosphorous ) Tj 3.869444 0 Td 59.953704 Tz (atom ) Tj 1.633333 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 46.990741 Tz (either ) Tj 1.827778 0 Td 47.530864 Tz (Substrate ) Tj 2.722222 0 Td 52.391975 Tz (within ) Tj 51.428571 0 0 51.428571 0 526.336196 Tm 6.358333 0 Td 51.851852 Tz (a ) Tj 0.563889 0 Td 51.527778 Tz (reasonable ) Tj 3.305556 0 Td 50.231481 Tz (distance ) Tj 2.566667 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 57.685185 Tz (T210, ) Tj 1.963889 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 45.730453 Tz (catalytic ) Tj 2.741667 0 Td 49.537037 Tz (residue ) Tj 2.294444 0 Td 59.953704 Tz (respon ) Tj 51.428571 0 0 51.428571 0 488.425743 Tm 6.377778 0 Td 44.722222 Tz (sible ) Tj 1.555556 0 Td 48.611111 Tz (for ) Tj 1.05 0 Td 43.75 Tz (initiating ) Tj 2.8 0 Td 50.231481 Tz (hydrolysis ) Tj 3.227778 0 Td 59.953704 Tz (by ) Tj 0.933333 0 Td 55.555556 Tz (forming ) Tj 2.527778 0 Td 51.851852 Tz (a ) Tj 0.505556 0 Td 51.041667 Tz (covalent ) Tj 2.625 0 Td 61.574074 Tz (bond ) Tj 1.652778 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 446.94155 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 56.271044 Tz (phosphorous ) Tj 3.986111 0 Td 53.796296 Tz (atom. ) Tj 1.886111 0 Td 52.662037 Tz (This ) Tj 1.594444 0 Td 43.75 Tz (result ) Tj 1.866667 0 Td 60.493827 Tz (was ) Tj 1.341667 0 Td 49.259259 Tz (consistent ) Tj 3.188889 0 Td 53.472222 Tz (with ) Tj 1.575 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 407.511515 Tm 6.358333 0 Td 48.611111 Tz (report ) Tj 1.944444 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 47.890947 Tz (Substrate ) Tj 2.8 0 Td 49.789562 Tz (recognition ) Tj 3.5 0 Td 53.472222 Tz (elements ) Tj 2.8 0 Td 48.070988 Tz (reside ) Tj 1.944444 0 Td 50.462963 Tz (outside ) Tj 2.294444 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 367.232274 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.625 0 Td 55.555556 Tz (domain. ) Tj 2.527778 0 Td 54.444444 Tz (Poses ) Tj 1.769444 0 Td 48.935185 Tz (consistent ) Tj 3.111111 0 Td 51.851852 Tz (with ) Tj 1.438889 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 45.37037 Tz (role ) Tj 1.244444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 73.45679 Tz (LPC ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 61.574074 Tz (an ) Tj 40 0 0 40 0 334 Tm 8.175 0 Td 101.388889 Tz (ATX ) Tj 2.2 0 Td 61.574074 Tz (substrate ) Tj 3.7 0 Td 76.041667 Tz (were ) Tj 2.2 0 Td 58.75 Tz (identified ) Tj 3.9 0 Td 83.333333 Tz (when ) Tj 2.375 0 Td 72.916667 Tz (an ) Tj 1.275 0 Td 64.880952 Tz (anionic ) Tj 3.1 0 Td 77.083333 Tz (atom ) Tj 2.25 0 Td 80.555556 Tz (was ) Tj 58.571429 0 0 58.571429 0 289.529851 Tm 5.565854 0 Td 45.172764 Tz (required ) Tj 2.304878 0 Td 41.260163 Tz (to ) Tj 0.665854 0 Td 48.373984 Tz (occur ) Tj 1.570732 0 Td 45.528455 Tz (within ) Tj 1.809756 0 Td 48.373984 Tz (a ) Tj 0.443902 0 Td 44.579946 Tz (3.6 ) Tj 0.973171 0 Td 76.829268 Tz (A ) Tj 0.597561 0 Td 46.95122 Tz (sphere ) Tj 1.826829 0 Td 45.884146 Tz (centered ) Tj 2.321951 0 Td 45.528455 Tz (4.6 ) Tj 0.973171 0 Td 76.829268 Tz (A ) Tj 0.631707 0 Td 51.930894 Tz (from ) Tj 58.571429 0 0 58.571429 0 249.045455 Tm 5.565854 0 Td 48.373984 Tz (both ) Tj 1.280488 0 Td 48.057814 Tz (metalions ) Tj 2.697561 0 Td 52.168022 Tz (and ) Tj 1.007317 0 Td 44.579946 Tz (2.8 ) Tj 0.956098 0 Td 71.138211 Tz (A ) Tj 0.529268 0 Td 52.642276 Tz (from ) Tj 1.382927 0 Td 42.682927 Tz (the ) Tj 0.904878 0 Td 54.065041 Tz (oxygenatom ) Tj 3.380488 0 Td 45.528455 Tz (of ) Tj 0.597561 0 Td 50.081301 Tz (T210. ) Tj 1.604878 0 Td 56.910569 Tz (The ) Tj 58.571429 0 0 58.571429 0 211.766119 Tm 5.565854 0 Td 49.92609 Tz (phosphorous ) Tj 3.482927 0 Td 52.642276 Tz (atom ) Tj 1.485366 0 Td 31.869919 Tz (still ) Tj 1.143902 0 Td 43.631436 Tz (preferred ) Tj 2.560976 0 Td 48.373984 Tz (a ) Tj 0.495122 0 Td 42.682927 Tz (location ) Tj 2.270732 0 Td 46.476965 Tz (6-7 ) Tj 1.041463 0 Td 76.829268 Tz (A ) Tj 0.64878 0 Td 51.219512 Tz (from ) Tj 1.468293 0 Td 42.682927 Tz (the ) Tj 51.428571 0 0 51.428571 0 170.873786 Tm 6.358333 0 Td 59.953704 Tz (oxygen ) Tj 2.313889 0 Td 59.953704 Tz (atom ) Tj 1.633333 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 57.037037 Tz (T210. ) Tj 30 0 0 30 0 2755 Tm 41.833333 0 Td 72.222222 Tz (5 ) 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 32.9 0 Td 69.369369 Tz (6 ) Tj 51.428571 0 0 51.428571 0 2915.986129 Tm 26.036111 0 Td 48.611111 Tz (In ) Tj 0.719444 0 Td 49.074074 Tz (greater ) Tj 2.197222 0 Td 42.12963 Tz (detail, ) Tj 1.886111 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 59.62963 Tz (model ) Tj 1.925 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 66.111111 Tz (human ) Tj 2.080556 0 Td 78.858025 Tz (ATX ) Tj 1.555556 0 Td 60.493827 Tz (was ) Tj 1.263889 0 Td 55.092593 Tz (developed ) Tj 3.111111 0 Td 59.953704 Tz (by ) Tj 51.428571 0 0 51.428571 0 2877.036662 Tm 25.277778 0 Td 61.574074 Tz (homology ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 0.991667 0 Td 50.771605 Tz (the ) Tj 1.322222 0 Td 65.895062 Tz (Xac ) Tj 1.633333 0 Td 50.555556 Tz (nucleotide ) Tj 3.422222 0 Td 56.064815 Tz (pyrophosphatase/phos ) Tj 51.428571 0 0 51.428571 0 2833.762999 Tm 25.297222 0 Td 50.854701 Tz (phodiesterase ) Tj 4.122222 0 Td 59.62963 Tz (\(NPP\) ) Tj 1.944444 0 Td 45.37037 Tz (crystal ) Tj 2.061111 0 Td 47.530864 Tz (structure ) Tj 2.722222 0 Td 46.990741 Tz (\(entry ) Tj 1.866667 0 Td 75.617284 Tz (2CSU31 ) Tj 3.169444 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2789.331725 Tm 25.316667 0 Td 49.074074 Tz (Protein ) Tj 2.275 0 Td 55.092593 Tz (Data ) Tj 1.555556 0 Td 52.391975 Tz (Bank\). ) Tj 2.061111 0 Td 62.654321 Tz (The ) Tj 1.283333 0 Td 55.902778 Tz (sequence ) Tj 2.838889 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 65.462963 Tz (human ) Tj 2.1 0 Td 77.777778 Tz (ATX ) Tj 1.575 0 Td 62.384259 Tz (\(GenBank ) Tj 51.428571 0 0 51.428571 0 2750.254408 Tm 25.297222 0 Td 49.259259 Tz (entry ) Tj 1.730556 0 Td 62.037037 Tz (Q13822\) ) Tj 2.819444 0 Td 62.654321 Tz (was ) Tj 1.380556 0 Td 50.925926 Tz (aligned ) Tj 2.372222 0 Td 54.282407 Tz (with ) Tj 1.555556 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 55.497685 Tz (sequence ) Tj 2.877778 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 65.895062 Tz (Xac ) Tj 1.419444 0 Td 74.537037 Tz (NPP ) Tj 51.428571 0 0 51.428571 0 2705.795152 Tm 25.277778 0 Td 53.148148 Tz (using ) Tj 1.730556 0 Td 89.660494 Tz (MOE ) Tj 1.730556 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 60.277778 Tz (amino ) Tj 1.925 0 Td 50.555556 Tz (acids ) Tj 1.711111 0 Td 52.5 Tz (1-161 ) Tj 1.75 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 56.481481 Tz (540-863 ) Tj 2.547222 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 75.617284 Tz (ATX ) Tj 1.516667 0 Td 59.143519 Tz (were ) Tj 51.428571 0 0 51.428571 0 2666.188769 Tm 25.297222 0 Td 50 Tz (deleted ) Tj 2.216667 0 Td 50.231481 Tz (as ) Tj 0.719444 0 Td 51.041667 Tz (they ) Tj 1.380556 0 Td 50.771605 Tz (did ) Tj 1.05 0 Td 50.771605 Tz (not ) Tj 1.030556 0 Td 53.796296 Tz (correspond ) Tj 3.305556 0 Td 48.611111 Tz (to ) Tj 0.680556 0 Td 61.574074 Tz (amino ) Tj 1.944444 0 Td 49.907407 Tz (acids ) Tj 1.652778 0 Td 51.851852 Tz (contained ) Tj 2.936111 0 Td 46.990741 Tz (in ) Tj 51.428571 0 0 51.428571 0 2623.730496 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 73.45679 Tz (XacNPP ) Tj 2.722222 0 Td 45.046296 Tz (structure. ) Tj 2.838889 0 Td 62.654321 Tz (The ) Tj 1.225 0 Td 76.697531 Tz (ATX ) Tj 1.516667 0 Td 59.62963 Tz (model ) Tj 1.905556 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 51.041667 Tz (then ) Tj 1.361111 0 Td 52.211934 Tz (generated ) Tj 2.916667 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 2584.531052 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.166667 0 Td 61.168981 Tz (homology ) Tj 3.227778 0 Td 59.62963 Tz (model ) Tj 2.041667 0 Td 50.231481 Tz (function ) Tj 2.683333 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 75.347222 Tz (MOE, ) Tj 2.041667 0 Td 59.41358 Tz (and ) Tj 1.341667 0 Td 47.395833 Tz (divalent ) Tj 2.586111 0 Td 52.5 Tz (metal ) Tj 51.428571 0 0 51.428571 0 2545.100122 Tm 25.297222 0 Td 48.611111 Tz (cations ) Tj 2.275 0 Td 59.143519 Tz (were ) Tj 1.613889 0 Td 48.316498 Tz (transferred ) Tj 3.383333 0 Td 46.990741 Tz (to ) Tj 0.797222 0 Td 53.596866 Tz (corresponding ) Tj 4.394444 0 Td 48.251029 Tz (locations ) Tj 2.858333 0 Td 43.75 Tz (in ) Tj 0.738889 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2504.981413 Tm 25.297222 0 Td 58.333333 Tz (from ) Tj 1.633333 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 65.895062 Tz (Xac ) Tj 1.380556 0 Td 75.617284 Tz (NPP ) Tj 1.536111 0 Td 45.833333 Tz (crystal ) Tj 2.119444 0 Td 45.046296 Tz (structure. ) Tj 2.955556 0 Td 47.962963 Tz (Ionization ) Tj 3.130556 0 Td 44.290123 Tz (states ) Tj 1.788889 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 59.41358 Tz (his ) Tj 51.428571 0 0 51.428571 0 2465.25 Tm 25.277778 0 Td 46.990741 Tz (tidine ) Tj 1.925 0 Td 49.016204 Tz (residues ) Tj 2.625 0 Td 51.851852 Tz (near ) Tj 1.438889 0 Td 48.206019 Tz (divalent ) Tj 2.547222 0 Td 51.851852 Tz (metal ) Tj 1.827778 0 Td 48.611111 Tz (cations ) Tj 2.294444 0 Td 57.523148 Tz (were ) Tj 1.613889 0 Td 50.636574 Tz (adjusted ) Tj 2.644444 0 Td 45.37037 Tz (to ) Tj 51.428571 0 0 51.428571 0 2428.967328 Tm 25.297222 0 Td 51.851852 Tz (Zero ) Tj 1.380556 0 Td 49.537037 Tz (charge, ) Tj 2.197222 0 Td 54.282407 Tz (with ) Tj 1.380556 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 52.662037 Tz (deprotonated ) Tj 3.908333 0 Td 53.292181 Tz (imidazole ) Tj 3.013889 0 Td 49.826389 Tz (nitrogen ) Tj 2.508333 0 Td 49.074074 Tz (nearest ) Tj 51.428571 0 0 51.428571 0 2386.263158 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 46.759259 Tz (cation. ) Tj 2.158333 0 Td 64.814815 Tz (The ) Tj 1.380556 0 Td 47.962963 Tz (ionization ) Tj 3.091667 0 Td 44.722222 Tz (state ) Tj 1.536111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 64.814815 Tz (T210 ) Tj 1.75 0 Td 62.654321 Tz (was ) Tj 1.302778 0 Td 51.041667 Tz (adjusted ) Tj 2.663889 0 Td 45.37037 Tz (to ) Tj 0.797222 0 Td 49.691358 Tz (-1, ) Tj 51.428571 0 0 51.428571 0 2347.473952 Tm 25.297222 0 Td 48.611111 Tz (consistent ) Tj 3.091667 0 Td 53.472222 Tz (with ) Tj 1.477778 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 76.157407 Tz (pH ) Tj 1.088889 0 Td 45.37037 Tz (profile ) Tj 2.080556 0 Td 54.552469 Tz (demonstrated ) Tj 4.122222 0 Td 47.530864 Tz (for ) Tj 0.991667 0 Td 65.895062 Tz (Xac ) Tj 1.380556 0 Td 58.333333 Tz (NPP. ) Tj 51.428571 0 0 51.428571 0 2309.185567 Tm 26.016667 0 Td 60.493827 Tz (Complexes ) Tj 3.5 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 77.777778 Tz (ATX ) Tj 1.652778 0 Td 52.662037 Tz (with ) Tj 1.536111 0 Td 51.851852 Tz (small ) Tj 1.847222 0 Td 53.652263 Tz (molecules ) Tj 3.169444 0 Td 50.771605 Tz (including ) Tj 2.975 0 Td 69.135802 Tz (sub ) Tj 51.428571 0 0 51.428571 0 2268.433414 Tm 25.316667 0 Td 42.12963 Tz (strates, ) Tj 2.255556 0 Td 44.781145 Tz (inhibitors, ) Tj 3.188889 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 51.851852 Tz (candidate ) Tj 3.033333 0 Td 44.486532 Tz (inhibitors, ) Tj 3.208333 0 Td 58.333333 Tz (were ) Tj 1.613889 0 Td 53.292181 Tz (generated ) Tj 51.428571 0 0 51.428571 0 2229.381071 Tm 25.277778 0 Td 61.574074 Tz (by ) Tj 0.972222 0 Td 55.555556 Tz (docking ) Tj 2.547222 0 Td 52.5 Tz (using ) Tj 1.788889 0 Td 72.106481 Tz (MOE. ) Tj 2.041667 0 Td 57.523148 Tz (Each ) Tj 1.594444 0 Td 51.851852 Tz (small ) Tj 1.808333 0 Td 55.497685 Tz (molecule ) Tj 2.877778 0 Td 46.8107 Tz (structure ) Tj 2.741667 0 Td 61.574074 Tz (was ) Tj 51.428571 0 0 51.428571 0 2189.829733 Tm 25.297222 0 Td 50.968013 Tz (constructed ) Tj 3.597222 0 Td 45.37037 Tz (in ) Tj 0.797222 0 Td 51.851852 Tz (the ) Tj 1.166667 0 Td 47.962963 Tz (ionization ) Tj 3.130556 0 Td 44.722222 Tz (state ) Tj 1.555556 0 Td 54.282407 Tz (expected ) Tj 2.819444 0 Td 45.37037 Tz (at ) Tj 0.777778 0 Td 74.537037 Tz (pH ) Tj 1.127778 0 Td 43.75 Tz (7. ) Tj 0.816667 0 Td 69.675926 Tz (Func ) Tj 51.428571 0 0 51.428571 0 2151.113831 Tm 25.277778 0 Td 46.450617 Tz (tional ) Tj 1.827778 0 Td 55.632716 Tz (groups ) Tj 2.177778 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 68.055556 Tz (pKa ) Tj 1.438889 0 Td 49.691358 Tz (values ) Tj 1.983333 0 Td 52.662037 Tz (near ) Tj 1.419444 0 Td 49.691358 Tz (seven, ) Tj 1.963889 0 Td 55.092593 Tz (such ) Tj 1.497222 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 54.73251 Tz (phosphate ) Tj 51.428571 0 0 51.428571 0 2112.209756 Tm 25.297222 0 Td 52.73569 Tz (monoesters, ) Tj 3.733333 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 52.662037 Tz (deprotonated ) Tj 4.005556 0 Td 58.333333 Tz (due ) Tj 1.244444 0 Td 46.990741 Tz (to ) Tj 0.777778 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 54.282407 Tz (expected ) Tj 2.819444 0 Td 50.925926 Tz (anionic ) Tj 51.428571 0 0 51.428571 0 2070.658537 Tm 25.316667 0 Td 45.121083 Tz (stabilization ) Tj 3.713889 0 Td 53.472222 Tz (provided ) Tj 2.722222 0 Td 61.574074 Tz (by ) Tj 0.933333 0 Td 48.611111 Tz (the ) Tj 1.011111 0 Td 48.611111 Tz (active ) Tj 1.925 0 Td 41.319444 Tz (site ) Tj 1.186111 0 Td 51.851852 Tz (metal ) Tj 1.769444 0 Td 45.37037 Tz (ions. ) Tj 1.594444 0 Td 53.877315 Tz (Residues ) Tj 47.142857 0 0 47.142857 0 2038 Tm 27.575758 0 Td 59.217172 Tz (with ) Tj 1.69697 0 Td 63.636364 Tz (atoms ) Tj 2.142424 0 Td 57.154882 Tz (within ) Tj 2.333333 0 Td 53.030303 Tz (6.5 ) Tj 1.251515 0 Td 91.919192 Tz (A ) Tj 0.827273 0 Td 65.40404 Tz (of ) Tj 0.954545 0 Td 53.030303 Tz (the ) Tj 1.187879 0 Td 52.441077 Tz (active ) Tj 2.142424 0 Td 46.843434 Tz (site ) Tj 1.4 0 Td 57.979798 Tz (metal ) Tj 2.036364 0 Td 53.914141 Tz (ions ) Tj 1.569697 0 Td 64.520202 Tz (were ) Tj 51.428571 0 0 51.428571 0 1992.508642 Tm 25.297222 0 Td 51.388889 Tz (defined ) Tj 2.333333 0 Td 51.851852 Tz (as ) Tj 0.855556 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 56.17284 Tz (placement ) Tj 3.247222 0 Td 38.888889 Tz (site. ) Tj 1.4 0 Td 55.740741 Tz (Small ) Tj 1.925 0 Td 54.012346 Tz (molecules ) Tj 3.15 0 Td 58.333333 Tz (were ) Tj 1.613889 0 Td 52.932099 Tz (placed ) Tj 51.428571 0 0 51.428571 0 1954.989583 Tm 25.297222 0 Td 46.180556 Tz (into ) Tj 1.458333 0 Td 77.777778 Tz (ATX ) Tj 1.769444 0 Td 52.5 Tz (using ) Tj 1.925 0 Td 49.691358 Tz (the ) Tj 1.244444 0 Td 59.548611 Tz (alphaPMI ) Tj 3.208333 0 Td 55.812757 Tz (placement ) Tj 3.402778 0 Td 55.092593 Tz (method, ) Tj 2.702778 0 Td 58.981481 Tz (which ) Tj 51.428571 0 0 51.428571 0 1912.321909 Tm 25.297222 0 Td 56.481481 Tz (matches ) Tj 2.566667 0 Td 50.771605 Tz (the ) Tj 1.147222 0 Td 51.203704 Tz (Small ) Tj 1.769444 0 Td 55.497685 Tz (molecule ) Tj 2.838889 0 Td 48.611111 Tz (principle ) Tj 2.838889 0 Td 62.962963 Tz (moments ) Tj 2.858333 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 44.444444 Tz (inertia ) Tj 2.061111 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 1875.921951 Tm 25.297222 0 Td 52.5 Tz (alpha ) Tj 1.788889 0 Td 51.388889 Tz (spheres ) Tj 2.372222 0 Td 47.138047 Tz (distributed ) Tj 3.325 0 Td 45.37037 Tz (in ) Tj 0.777778 0 Td 48.148148 Tz (closely ) Tj 2.255556 0 Td 57.253086 Tz (packed ) Tj 2.255556 0 Td 48.251029 Tz (locations ) Tj 2.838889 0 Td 51.851852 Tz (within ) Tj 51.428571 0 0 51.428571 0 1834.721154 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 55.555556 Tz (docking ) Tj 2.469444 0 Td 38.888889 Tz (site. ) Tj 1.322222 0 Td 56.388889 Tz (Small ) Tj 1.866667 0 Td 55.497685 Tz (molecule ) Tj 2.8 0 Td 53.148148 Tz (poses ) Tj 1.75 0 Td 59.143519 Tz (were ) Tj 1.555556 0 Td 52.932099 Tz (scored ) Tj 2.041667 0 Td 52.5 Tz (using ) Tj 1.711111 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 1797.294331 Tm 25.297222 0 Td 42.939815 Tz (affinity ) Tj 2.138889 0 Td 81.018519 Tz (DG ) Tj 1.205556 0 Td 47.530864 Tz (function, ) Tj 2.780556 0 Td 58.981481 Tz (which ) Tj 1.983333 0 Td 54.282407 Tz (approximates ) Tj 4.141667 0 Td 48.611111 Tz (the ) Tj 1.030556 0 Td 49.691358 Tz (enthalpic ) Tj 2.897222 0 Td 71.296296 Tz (con ) Tj 51.428571 0 0 51.428571 0 1756.074663 Tm 25.277778 0 Td 46.090535 Tz (tribution ) Tj 2.722222 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 53.240741 Tz (binding ) Tj 2.430556 0 Td 47.800926 Tz (free ) Tj 1.322222 0 Td 49.537037 Tz (energy. ) Tj 2.313889 0 Td 53.472222 Tz (This ) Tj 1.516667 0 Td 54.79798 Tz (combination ) Tj 3.830556 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 59.62963 Tz (place ) Tj 51.428571 0 0 51.428571 0 1716.727273 Tm 25.297222 0 Td 60.763889 Tz (ment ) Tj 1.594444 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 50.925926 Tz (scoring ) Tj 2.313889 0 Td 57.87037 Tz (methods ) Tj 2.586111 0 Td 60.493827 Tz (was ) Tj 1.263889 0 Td 48.611111 Tz (selected ) Tj 2.469444 0 Td 55.092593 Tz (based ) Tj 1.808333 0 Td 58.333333 Tz (on ) Tj 0.855556 0 Td 56.712963 Tz (comparison ) Tj 51.428571 0 0 51.428571 0 1678.180268 Tm 25.297222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 45.37037 Tz (results ) Tj 2.061111 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 58.333333 Tz (two ) Tj 1.263889 0 Td 42.939815 Tz (test ) Tj 1.205556 0 Td 51.041667 Tz (systems. ) Tj 2.644444 0 Td 62.654321 Tz (The ) Tj 1.302778 0 Td 59.548611 Tz (alphaDMI ) Tj 3.033333 0 Td 56.17284 Tz (placement ) Tj 3.169444 0 Td 60.493827 Tz (and ) Tj 52.857143 0 0 52.857143 0 1638.618267 Tm 24.613514 0 Td 52.815315 Tz (affinityDGenergy ) Tj 5.202703 0 Td 49.268018 Tz (function ) Tj 2.478378 0 Td 57.545045 Tz (were ) Tj 1.513514 0 Td 54.864865 Tz (found ) Tj 1.759459 0 Td 45.720721 Tz (to ) Tj 0.681081 0 Td 52.552553 Tz (reproduce ) Tj 2.932432 0 Td 49.399399 Tz (the ) Tj 1.002703 0 Td 59.121622 Tz (crys ) Tj 51.428571 0 0 51.428571 0 1598.706444 Tm 25.277778 0 Td 48.341049 Tz (tallographic ) Tj 3.616667 0 Td 49.016204 Tz (position ) Tj 2.488889 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 48.112536 Tz (rosiglitazone ) Tj 3.888889 0 Td 45.37037 Tz (in ) Tj 0.719444 0 Td 67.407407 Tz (PPARY ) Tj 2.158333 0 Td 50.231481 Tz (as ) Tj 0.758333 0 Td 51.851852 Tz (well ) Tj 1.380556 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 56.17284 Tz (our ) Tj 51.428571 0 0 51.428571 0 1560.817308 Tm 25.297222 0 Td 51.446759 Tz (previous ) Tj 2.722222 0 Td 57.79321 Tz (docked ) Tj 2.275 0 Td 48.611111 Tz (position ) Tj 2.547222 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 52.73569 Tz (sphingosine ) Tj 3.752778 0 Td 52.73569 Tz (1-phosphate ) Tj 3.713889 0 Td 54.444444 Tz (\(S1P\) ) Tj 51.428571 0 0 51.428571 0 1517.635417 Tm 25.277778 0 Td 51.851852 Tz (within ) Tj 2.158333 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 48.611111 Tz (validated ) Tj 2.916667 0 Td 59.62963 Tz (model ) Tj 2.061111 0 Td 61.574074 Tz (of ) Tj 0.913889 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 66.975309 Tz (S1P ) Tj 1.788889 0 Td 45.010288 Tz (receptor. ) Tj 2.780556 0 Td 59.259259 Tz (Docking ) Tj 51.428571 0 0 51.428571 0 1477.390453 Tm 25.316667 0 Td 50.378788 Tz (simulations ) Tj 3.538889 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 51.851852 Tz (Small ) Tj 1.808333 0 Td 54.372428 Tz (molecules ) Tj 3.130556 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 54.282407 Tz (long ) Tj 1.477778 0 Td 48.611111 Tz (alkyl ) Tj 1.652778 0 Td 51.311728 Tz (chains ) Tj 2.041667 0 Td 63.194444 Tz (addi ) Tj 51.428571 0 0 51.428571 0 1439.844282 Tm 25.277778 0 Td 46.585648 Tz (tionally ) Tj 2.430556 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 56.17284 Tz (performed ) Tj 3.227778 0 Td 50.231481 Tz (multiple ) Tj 2.605556 0 Td 51.851852 Tz (times ) Tj 1.75 0 Td 58.333333 Tz (due ) Tj 1.225 0 Td 45.37037 Tz (to ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 47.314815 Tz (stochastic ) Tj 51.428571 0 0 51.428571 0 1400.080214 Tm 25.297222 0 Td 50.771605 Tz (nature ) Tj 2.333333 0 Td 58.333333 Tz (of ) Tj 1.108333 0 Td 50.771605 Tz (the ) Tj 1.419444 0 Td 52.546296 Tz (conformational ) Tj 4.958333 0 Td 55.497685 Tz (sampling ) Tj 3.15 0 Td 54.372428 Tz (procedure ) Tj 3.422222 0 Td 60.493827 Tz (and ) Tj 51.428571 0 0 51.428571 0 1358.64277 Tm 25.297222 0 Td 51.851852 Tz (included ) Tj 2.722222 0 Td 55.092593 Tz (an ) Tj 0.894444 0 Td 51.131687 Tz (increased ) Tj 3.013889 0 Td 61.033951 Tz (number ) Tj 2.411111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 55.555556 Tz (samples ) Tj 2.566667 0 Td 52.932099 Tz (per ) Tj 1.147222 0 Td 54.552469 Tz (conformation ) Tj 51.428571 0 0 51.428571 0 1320.174142 Tm 25.316667 0 Td 49.421296 Tz (\(50\) ) Tj 1.497222 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 58.333333 Tz (an ) Tj 1.030556 0 Td 50.771605 Tz (increased ) Tj 3.052778 0 Td 62.114198 Tz (number ) Tj 2.508333 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 53.796296 Tz (poses ) Tj 1.925 0 Td 51.851852 Tz (\(500\) ) Tj 1.886111 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 56.944444 Tz (improve ) Tj 51.428571 0 0 51.428571 0 1280.264151 Tm 25.316667 0 Td 51.851852 Tz (sampling. ) Tj 2.975 0 Td 55.840456 Tz (Conformations ) Tj 4.530556 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 50.555556 Tz (these ) Tj 1.633333 0 Td 51.851852 Tz (highly ) Tj 2.061111 0 Td 44.965278 Tz (flexible ) Tj 2.333333 0 Td 54.012346 Tz (molecules ) Tj 51.428571 0 0 51.428571 0 1242.945879 Tm 25.277778 0 Td 59.953704 Tz (were ) Tj 1.633333 0 Td 48.611111 Tz (also ) Tj 1.380556 0 Td 57.744108 Tz (precomputed ) Tj 4.005556 0 Td 46.990741 Tz (in ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 55.092593 Tz (absence ) Tj 2.527778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.108333 0 Td 50.231481 Tz (receptor ) Tj 2.586111 0 Td 52.5 Tz (using ) Tj 51.428571 0 0 51.428571 0 1200.361702 Tm 25.277778 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 47.314815 Tz (stochastic ) Tj 2.994444 0 Td 52.546296 Tz (conformational ) Tj 4.569444 0 Td 50.771605 Tz (search ) Tj 1.983333 0 Td 51.851852 Tz (algorithm ) Tj 2.936111 0 Td 60.493827 Tz (and ) Tj 1.205556 0 Td 39.969136 Tz (all ) Tj 0.875 0 Td 51.311728 Tz (result ) Tj 51.428571 0 0 51.428571 0 1162.606635 Tm 25.297222 0 Td 52.932099 Tz (ing ) Tj 1.069444 0 Td 53.596866 Tz (conformations ) Tj 4.316667 0 Td 58.333333 Tz (were ) Tj 1.536111 0 Td 45.37037 Tz (rigidly ) Tj 2.061111 0 Td 57.79321 Tz (docked ) Tj 2.197222 0 Td 46.990741 Tz (into ) Tj 1.244444 0 Td 50.771605 Tz (the ) Tj 1.030556 0 Td 46.090535 Tz (receptor. ) Tj 2.644444 0 Td 75.617284 Tz (Sub ) Tj 51.428571 0 0 51.428571 0 1124.125471 Tm 25.316667 0 Td 43.209877 Tz (strate ) Tj 1.808333 0 Td 56.018519 Tz (docking ) Tj 2.605556 0 Td 47.685185 Tz (studies ) Tj 2.275 0 Td 59.143519 Tz (were ) Tj 1.633333 0 Td 56.893004 Tz (performed ) Tj 3.325 0 Td 45.37037 Tz (in ) Tj 0.797222 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 53.472222 Tz (presence ) Tj 2.819444 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 1082.424084 Tm 25.297222 0 Td 55.092593 Tz (absence ) Tj 2.605556 0 Td 58.333333 Tz (of ) Tj 0.913889 0 Td 55.092593 Tz (a ) Tj 0.622222 0 Td 44.290123 Tz (restraint ) Tj 2.702778 0 Td 48.971193 Tz (requiring ) Tj 2.955556 0 Td 55.092593 Tz (an ) Tj 0.952778 0 Td 51.388889 Tz (anionic ) Tj 2.469444 0 Td 59.953704 Tz (atom ) Tj 1.730556 0 Td 48.611111 Tz (to ) Tj 0.913889 0 Td 54.444444 Tz (occur ) Tj 58.571429 0 0 58.571429 0 1042.060753 Tm 22.212195 0 Td 43.157182 Tz (inside ) Tj 1.639024 0 Td 45.528455 Tz (a ) Tj 0.392683 0 Td 44.579946 Tz (3.6 ) Tj 0.939024 0 Td 73.98374 Tz (A ) Tj 0.580488 0 Td 46.00271 Tz (sphere ) Tj 1.758537 0 Td 45.172764 Tz (centered ) Tj 2.270732 0 Td 45.528455 Tz (4.6 ) Tj 0.921951 0 Td 76.829268 Tz (A ) Tj 0.597561 0 Td 50.50813 Tz (from ) Tj 1.34878 0 Td 46.95122 Tz (both ) Tj 1.263415 0 Td 48.057814 Tz (metalions ) Tj 2.697561 0 Td 52.168022 Tz (and ) Tj 58.571429 0 0 58.571429 0 1004.109375 Tm 22.212195 0 Td 43.631436 Tz (2.8 ) Tj 1.007317 0 Td 76.829268 Tz (A ) Tj 0.64878 0 Td 49.796748 Tz (from ) Tj 1.4 0 Td 44.579946 Tz (the ) Tj 0.973171 0 Td 52.168022 Tz (oxygen ) Tj 2.065854 0 Td 52.642276 Tz (atom ) Tj 1.468293 0 Td 49.796748 Tz (of ) Tj 0.7 0 Td 49.512195 Tz (T210. ) Tj 1.707317 0 Td 44.105691 Tz (In ) Tj 0.7 0 Td 35.094851 Tz (all ) Tj 0.836585 0 Td 41.260163 Tz (cases, ) Tj 1.690244 0 Td 44.579946 Tz (the ) Tj 0.939024 0 Td 49.796748 Tz (pose ) Tj 51.428571 0 0 51.428571 0 963.728395 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 52.391975 Tz (lowest ) Tj 2.080556 0 Td 52.5 Tz (score ) Tj 1.730556 0 Td 46.018519 Tz (after ) Tj 1.555556 0 Td 50.084175 Tz (elimination ) Tj 3.519444 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 49.691358 Tz (ligand ) Tj 1.983333 0 Td 53.796296 Tz (poses ) Tj 1.866667 0 Td 53.472222 Tz (with ) Tj 51.428571 0 0 51.428571 0 924.148325 Tm 25.316667 0 Td 47.800926 Tz (strained ) Tj 2.469444 0 Td 53.596866 Tz (conformations ) Tj 4.375 0 Td 60.493827 Tz (was ) Tj 1.283333 0 Td 48.611111 Tz (selected ) Tj 2.508333 0 Td 48.611111 Tz (for ) Tj 1.011111 0 Td 48.611111 Tz (analysis ) Tj 2.488889 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 57.253086 Tz (discus ) Tj 27.142857 0 0 27.142857 0 891 Tm 47.968421 0 Td 105.921053 Tz (S1O. ) Tj 51.428571 0 0 51.428571 0 847.793282 Tm 26.016667 0 Td 53.472222 Tz (This ) Tj 1.497222 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 45.37037 Tz (catalytic ) Tj 2.702778 0 Td 59.953704 Tz (domain ) Tj 2.391667 0 Td 61.574074 Tz (homology ) Tj 3.208333 0 Td 59.62963 Tz (model ) Tj 2.041667 0 Td 53.472222 Tz (was, ) Tj 1.516667 0 Td 48.070988 Tz (again, ) Tj 51.428571 0 0 51.428571 0 808.597813 Tm 25.277778 0 Td 51.041667 Tz (thus ) Tj 1.419444 0 Td 54.282407 Tz (used ) Tj 1.438889 0 Td 51.851852 Tz (as ) Tj 0.777778 0 Td 58.333333 Tz (a ) Tj 0.486111 0 Td 56.018519 Tz (docking ) Tj 2.508333 0 Td 45.37037 Tz (target ) Tj 1.808333 0 Td 45.37037 Tz (to ) Tj 0.719444 0 Td 46.990741 Tz (identify ) Tj 2.430556 0 Td 54.73251 Tz (promising ) Tj 3.130556 0 Td 51.131687 Tz (candidate ) Tj 51.428571 0 0 51.428571 0 769.33993 Tm 25.297222 0 Td 46.342593 Tz (inhibitors ) Tj 2.936111 0 Td 47.530864 Tz (for ) Tj 0.933333 0 Td 52.662037 Tz (experimental ) Tj 3.927778 0 Td 48.935185 Tz (Screening. ) Tj 3.091667 0 Td 40.740741 Tz (Initial ) Tj 1.847222 0 Td 48.611111 Tz (analysis ) Tj 2.469444 0 Td 54.62963 Tz (focused ) Tj 51.428571 0 0 51.428571 0 729.127811 Tm 25.297222 0 Td 59.953704 Tz (on ) Tj 0.855556 0 Td 50.462963 Tz (anionic ) Tj 2.236111 0 Td 55.092593 Tz (groups ) Tj 2.119444 0 Td 55.092593 Tz (such ) Tj 1.458333 0 Td 50.231481 Tz (as ) Tj 0.738889 0 Td 51.851852 Tz (phosphate, ) Tj 3.247222 0 Td 44.155093 Tz (Sulfate, ) Tj 2.236111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 51.262626 Tz (carboxylate ) Tj 51.428571 0 0 51.428571 0 688.520833 Tm 25.297222 0 Td 50.231481 Tz (as ) Tj 0.933333 0 Td 51.851852 Tz (well ) Tj 1.555556 0 Td 50.231481 Tz (as ) Tj 0.952778 0 Td 47.530864 Tz (bioisosteres ) Tj 3.772222 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 50.555556 Tz (these ) Tj 1.808333 0 Td 51.388889 Tz (anionic ) Tj 2.488889 0 Td 55.092593 Tz (groups ) Tj 2.333333 0 Td 50.411523 Tz (including ) Tj 51.428571 0 0 51.428571 0 650.733496 Tm 25.297222 0 Td 56.944444 Tz (phosphonamide, ) Tj 5.172222 0 Td 52.391975 Tz (Sulfonamide, ) Tj 4.141667 0 Td 59.41358 Tz (and ) Tj 1.458333 0 Td 51.419753 Tz (oxocarboxylate. ) Tj 5.036111 0 Td 91.820988 Tz (Com ) Tj 51.428571 0 0 51.428571 0 609.640587 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.275 0 Td 57.87037 Tz (showing ) Tj 2.547222 0 Td 47.530864 Tz (better ) Tj 1.847222 0 Td 51.041667 Tz (than ) Tj 1.4 0 Td 72.376543 Tz (50% ) Tj 1.438889 0 Td 77.777778 Tz (ATX ) Tj 1.536111 0 Td 46.990741 Tz (inhibition ) Tj 2.975 0 Td 45.37037 Tz (at ) Tj 0.758333 0 Td 56.712963 Tz (10 ) Tj 0.836111 0 Td 81.018519 Tz (uM ) Tj 1.108333 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 572.392157 Tm 25.297222 0 Td 63.194444 Tz (enzyme ) Tj 2.430556 0 Td 44.965278 Tz (activity ) Tj 2.352778 0 Td 51.851852 Tz (assay ) Tj 1.75 0 Td 59.143519 Tz (were ) Tj 1.575 0 Td 55.902778 Tz (used ) Tj 1.497222 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 46.342593 Tz (similarity ) Tj 2.955556 0 Td 45.833333 Tz (targets ) Tj 2.119444 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 69.135802 Tz (Sub ) Tj 51.428571 0 0 51.428571 0 532.199005 Tm 25.316667 0 Td 52.777778 Tz (sequent ) Tj 2.488889 0 Td 48.971193 Tz (analyses. ) Tj 2.975 0 Td 50.673401 Tz (Ninety-five ) Tj 3.636111 0 Td 46.666667 Tz (structures ) Tj 3.130556 0 Td 59.143519 Tz (were ) Tj 1.730556 0 Td 48.611111 Tz (selected ) Tj 2.644444 0 Td 48.611111 Tz (for ) Tj 51.428571 0 0 51.428571 0 492.274809 Tm 25.316667 0 Td 51.131687 Tz (screening ) Tj 3.052778 0 Td 51.851852 Tz (out ) Tj 1.186111 0 Td 59.953704 Tz (of ) Tj 0.933333 0 Td 61.574074 Tz (500 ) Tj 1.361111 0 Td 61.934156 Tz (compounds ) Tj 3.655556 0 Td 57.79321 Tz (docked ) Tj 2.372222 0 Td 49.074074 Tz (against ) Tj 2.352778 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 451.682809 Tm 25.297222 0 Td 45.37037 Tz (catalytic ) Tj 2.663889 0 Td 59.953704 Tz (domain ) Tj 2.352778 0 Td 61.168981 Tz (homology ) Tj 3.169444 0 Td 54.012346 Tz (model. ) Tj 2.177778 0 Td 35.648148 Tz (It ) Tj 0.602778 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 54.552469 Tz (demonstrated ) Tj 4.102778 0 Td 46.180556 Tz (that ) Tj 40 0 0 40 0 417 Tm 32.6 0 Td 70.833333 Tz (19 ) Tj 1.175 0 Td 72.916667 Tz (of ) Tj 1.075 0 Td 62.5 Tz (the ) Tj 1.425 0 Td 75 Tz (95 ) Tj 1.225 0 Td 60.416667 Tz (Structures ) Tj 3.975 0 Td 60.648148 Tz (inhibited ) Tj 3.625 0 Td 91.666667 Tz (20% ) Tj 1.975 0 Td 68.75 Tz (or ) Tj 1.125 0 Td 79.166667 Tz (more ) Tj 2.2 0 Td 72.916667 Tz (of ) Tj 1.05 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 116.666667 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 372.845509 Tm 25.297222 0 Td 50.771605 Tz (catalyzed ) Tj 2.897222 0 Td 55.902778 Tz (FS-3 ) Tj 1.477778 0 Td 50.555556 Tz (hydrolysis ) Tj 3.15 0 Td 45.37037 Tz (at ) Tj 0.719444 0 Td 53.472222 Tz (10 ) Tj 0.972222 0 Td 68.055556 Tz (LM ) Tj 0.894444 0 Td 49.074074 Tz (concentration. ) Tj 4.238889 0 Td 54.282407 Tz (This ) Tj 1.419444 0 Td 56.388889 Tz (selec ) Tj 51.428571 0 0 51.428571 0 332.465409 Tm 25.277778 0 Td 46.990741 Tz (tion ) Tj 1.4 0 Td 51.851852 Tz (process ) Tj 2.430556 0 Td 61.574074 Tz (was ) Tj 1.361111 0 Td 48.971193 Tz (therefore ) Tj 2.897222 0 Td 72.376543 Tz (20% ) Tj 1.555556 0 Td 51.041667 Tz (accurate ) Tj 2.683333 0 Td 46.990741 Tz (in ) Tj 0.836111 0 Td 47.890947 Tz (selecting ) Tj 2.819444 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 293.69281 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.275 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 64.814815 Tz (some ) Tj 1.730556 0 Td 53.472222 Tz (degree ) Tj 2.080556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 77.777778 Tz (ATX ) Tj 1.594444 0 Td 45.075758 Tz (inhibition. ) Tj 51.428571 0 0 51.428571 0 255.04472 Tm 26.036111 0 Td 59.722222 Tz (Docking ) Tj 2.663889 0 Td 47.222222 Tz (studies ) Tj 2.177778 0 Td 51.851852 Tz (with ) Tj 1.4 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 45.37037 Tz (catalytic ) Tj 2.605556 0 Td 60.493827 Tz (domain ) Tj 2.333333 0 Td 61.574074 Tz (homology ) Tj 51.428571 0 0 51.428571 0 213.122183 Tm 25.297222 0 Td 59.62963 Tz (model ) Tj 1.963889 0 Td 58.333333 Tz (were ) Tj 1.516667 0 Td 51.041667 Tz (able ) Tj 1.341667 0 Td 46.990741 Tz (to ) Tj 0.680556 0 Td 53.240741 Tz (provide ) Tj 2.352778 0 Td 47.685185 Tz (insight ) Tj 2.119444 0 Td 46.180556 Tz (into ) Tj 1.225 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 48.611111 Tz (differences ) Tj 3.344444 0 Td 58.333333 Tz (of ) Tj 51.428571 0 0 51.428571 0 170.682464 Tm 25.297222 0 Td 52.662037 Tz (very ) Tj 1.419444 0 Td 48.148148 Tz (similar ) Tj 2.119444 0 Td 45.075758 Tz (structures. ) Tj 3.130556 0 Td 55.902778 Tz (Very ) Tj 1.477778 0 Td 48.287037 Tz (Surprising ) Tj 2.994444 0 Td 45.37037 Tz (results ) Tj 2.041667 0 Td 58.333333 Tz (were ) Tj 1.555556 0 Td 48.611111 Tz (noted, ) Tj 1.905556 0 Td 47.530864 Tz (for ) Tj 1.428571 0 0 1.428571 0 2440 Tm 536.2 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 110 0 obj << /Length 1 >> stream q endstream endobj 111 0 obj << /Length 15106 >> 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 57.154882 Tz (8,268,891 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 51.428571 0 0 51.428571 0 2968 Tm 14.875 0 Td 77.777778 Tz (7 ) Tj 51.428571 0 0 51.428571 0 2916.06 Tm 6.358333 0 Td 54.282407 Tz (example, ) Tj 2.916667 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 58.333333 Tz (two ) Tj 1.322222 0 Td 46.090535 Tz (different ) Tj 2.741667 0 Td 49.331276 Tz (isoindole ) Tj 2.916667 0 Td 61.934156 Tz (compounds ) Tj 3.636111 0 Td 45.37037 Tz (that ) Tj 1.322222 0 Td 58.333333 Tz (dif ) Tj 51.428571 0 0 51.428571 0 2874.500736 Tm 6.358333 0 Td 49.907407 Tz (fered ) Tj 1.672222 0 Td 59.953704 Tz (by ) Tj 0.894444 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 48.611111 Tz (location ) Tj 2.527778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 52.662037 Tz (carboxyl ) Tj 2.702778 0 Td 55.555556 Tz (pendant ) Tj 2.508333 0 Td 51.311728 Tz (group: ) Tj 81.904762 0 0 81.904762 0 2717.051136 Tm 6.788372 0 Td 42.732558 Tz (O ) Tj 5.469767 0 Td 50.872093 Tz (Na ) Tj 1.343023 0 Td 213.662791 Tz (O ) Tj 31.428571 0 0 31.428571 0 2643 Tm 15.527273 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2614 Tm 25.422727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2501.896552 Tm 10.627273 0 Td 106.060606 Tz (HO ) Tj 14.636364 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2408 Tm 12.854545 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2378 Tm 23.036364 0 Td 76.515152 Tz (5564949 ) Tj 37.857143 0 0 37.857143 0 2248.73913 Tm 12.388679 0 Td 92.45283 Tz (O ) Tj 13.418868 0 Td 70.440252 Tz (Nin ) Tj 42.857143 0 0 42.857143 0 2226.277778 Tm 17.22 0 Td 81.666667 Tz (O ) Tj 6.113333 0 Td 128.333333 Tz (n ) Tj 31.428571 0 0 31.428571 0 2155 Tm 12.504545 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 2122 Tm 23.672727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 2010 Tm 23.481818 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1855 Tm 10.627273 0 Td 106.060606 Tz (HO ) Tj 4.295455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1813 Tm 23.036364 0 Td 76.515152 Tz (5564676 ) Tj 51.428571 0 0 51.428571 0 1738.54902 Tm 7.097222 0 Td 63.734568 Tz (The ) Tj 1.244444 0 Td 60.185185 Tz (5564949 ) Tj 2.663889 0 Td 64.00463 Tz (compound ) Tj 3.169444 0 Td 50.411523 Tz (exhibited ) Tj 2.819444 0 Td 58.333333 Tz (a ) Tj 0.447222 0 Td 74.537037 Tz (51% ) Tj 1.477778 0 Td 50.771605 Tz (reduction ) Tj 2.838889 0 Td 46.990741 Tz (in ) Tj 0.661111 0 Td 77.777778 Tz (ATX ) Tj 48.571429 0 0 48.571429 0 1697 Tm 6.732353 0 Td 49.754902 Tz (inhibition ) Tj 3.5 0 Td 46.323529 Tz (at ) Tj 1.132353 0 Td 60.04902 Tz (10 ) Tj 1.194118 0 Td 61.764706 Tz (micromole ) Tj 3.829412 0 Td 51.960784 Tz (concentration, ) Tj 4.879412 0 Td 59.803922 Tz (whereas ) Tj 3.026471 0 Td 52.614379 Tz (the ) Tj 51.428571 0 0 51.428571 0 1654.554736 Tm 6.377778 0 Td 59.722222 Tz (5564676 ) Tj 2.702778 0 Td 64.00463 Tz (compound ) Tj 3.247222 0 Td 61.033951 Tz (showed ) Tj 2.411111 0 Td 56.712963 Tz (no ) Tj 0.894444 0 Td 50.411523 Tz (reduction ) Tj 2.916667 0 Td 45.910494 Tz (levels ) Tj 1.827778 0 Td 45.37037 Tz (at ) Tj 0.680556 0 Td 41.049383 Tz (all ) Tj 0.933333 0 Td 44.290123 Tz (\(at ) Tj 0.952778 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1612.449344 Tm 6.377778 0 Td 61.574074 Tz (same ) Tj 1.672222 0 Td 48.179012 Tz (concentration\). ) Tj 4.511111 0 Td 55.092593 Tz (Thus, ) Tj 1.847222 0 Td 44.781145 Tz (selectivity ) Tj 3.130556 0 Td 57.87037 Tz (between ) Tj 2.625 0 Td 46.759259 Tz (certain ) Tj 2.158333 0 Td 83.179012 Tz (com ) Tj 51.428571 0 0 51.428571 0 1570.223529 Tm 6.358333 0 Td 54.166667 Tz (pounds, ) Tj 2.741667 0 Td 56.893004 Tz (sometimes ) Tj 3.519444 0 Td 46.990741 Tz (constitutional ) Tj 4.394444 0 Td 53.703704 Tz (isomers ) Tj 2.663889 0 Td 51.851852 Tz (even, ) Tj 2.002778 0 Td 60.493827 Tz (was ) Tj 1.555556 0 Td 56.712963 Tz (of ) Tj 51.428571 0 0 51.428571 0 1529.265589 Tm 6.377778 0 Td 49.331276 Tz (necessity ) Tj 2.780556 0 Td 45.37037 Tz (to ) Tj 0.661111 0 Td 54.372428 Tz (determine ) Tj 3.013889 0 Td 46.8107 Tz (effective ) Tj 2.625 0 Td 53.009259 Tz (ATXinhibitors. ) Tj 4.55 0 Td 65.895062 Tz (The ) Tj 1.283333 0 Td 60.185185 Tz (5564949 ) Tj 51.428571 0 0 51.428571 0 1489.758918 Tm 6.358333 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 47.800926 Tz (actually ) Tj 2.488889 0 Td 61.574074 Tz (was ) Tj 1.322222 0 Td 56.388889 Tz (found ) Tj 1.886111 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 49.074074 Tz (display ) Tj 2.255556 0 Td 58.333333 Tz (a ) Tj 0.544444 0 Td 62.114198 Tz (number ) Tj 2.391667 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 57.685185 Tz (favor ) Tj 51.428571 0 0 51.428571 0 1446.352406 Tm 6.358333 0 Td 51.041667 Tz (able ) Tj 1.516667 0 Td 46.990741 Tz (interactions ) Tj 3.675 0 Td 46.990741 Tz (in ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.147222 0 Td 58.333333 Tz (docked ) Tj 2.372222 0 Td 60.185185 Tz (complex ) Tj 2.819444 0 Td 45.37037 Tz (in ) Tj 0.855556 0 Td 53.796296 Tz (terms ) Tj 1.886111 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 1404.415758 Tm 6.358333 0 Td 43.013468 Tz (reactivity. ) Tj 3.072222 0 Td 59.62963 Tz (These ) Tj 2.022222 0 Td 46.990741 Tz (interactions ) Tj 3.655556 0 Td 50.462963 Tz (include ) Tj 2.372222 0 Td 55.092593 Tz (a ) Tj 0.563889 0 Td 45.010288 Tz (cation-It ) Tj 2.663889 0 Td 47.727273 Tz (interaction ) Tj 51.428571 0 0 51.428571 0 1363.562347 Tm 6.338889 0 Td 57.87037 Tz (between ) Tj 2.644444 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 51.557239 Tz (carboxylate ) Tj 3.597222 0 Td 48.935185 Tz (functional ) Tj 3.130556 0 Td 56.388889 Tz (group ) Tj 1.866667 0 Td 60.493827 Tz (and ) Tj 1.244444 0 Td 55.092593 Tz (8284, ) Tj 1.866667 0 Td 55.092593 Tz (an ) Tj 0.894444 0 Td 63.734568 Tz (ion ) Tj 51.428571 0 0 51.428571 0 1323.467609 Tm 6.358333 0 Td 49.074074 Tz (pairing ) Tj 2.216667 0 Td 46.843434 Tz (interaction ) Tj 3.247222 0 Td 57.87037 Tz (between ) Tj 2.586111 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 51.557239 Tz (carboxylate ) Tj 3.558333 0 Td 48.611111 Tz (functional ) Tj 3.091667 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 1279.1133 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 56.388889 Tz (R285, ) Tj 1.886111 0 Td 58.333333 Tz (and ) Tj 1.283333 0 Td 52.5 Tz (metal ) Tj 1.788889 0 Td 45.775463 Tz (ligating ) Tj 2.391667 0 Td 46.990741 Tz (interactions ) Tj 3.597222 0 Td 52.662037 Tz (with ) Tj 1.477778 0 Td 49.691358 Tz (the ) Tj 1.069444 0 Td 49.691358 Tz (isoindole ) Tj 51.428571 0 0 51.428571 0 1238.129771 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.361111 0 Td 49.331276 Tz (diazerine ) Tj 2.975 0 Td 48.935185 Tz (functional ) Tj 3.208333 0 Td 51.388889 Tz (groups. ) Tj 2.508333 0 Td 48.611111 Tz (In ) Tj 0.894444 0 Td 45.730453 Tz (contrast, ) Tj 2.780556 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 60.185185 Tz (5564676 ) Tj 51.428571 0 0 51.428571 0 1197.409756 Tm 6.358333 0 Td 45.910494 Tz (failed ) Tj 1.788889 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 59.953704 Tz (dock ) Tj 1.555556 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 76.697531 Tz (ATX ) Tj 1.555556 0 Td 44.650206 Tz (catalytic ) Tj 2.625 0 Td 59.41358 Tz (domain ) Tj 2.352778 0 Td 54.012346 Tz (model, ) Tj 2.138889 0 Td 56.944444 Tz (Suggest ) Tj 51.428571 0 0 51.428571 0 1157.307985 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.186111 0 Td 46.180556 Tz (that ) Tj 1.361111 0 Td 45.37037 Tz (insufficient ) Tj 3.538889 0 Td 53.148148 Tz (space ) Tj 1.886111 0 Td 61.574074 Tz (was ) Tj 1.341667 0 Td 48.611111 Tz (available ) Tj 2.897222 0 Td 47.530864 Tz (for ) Tj 1.069444 0 Td 44.560185 Tz (this ) Tj 1.361111 0 Td 51.851852 Tz (molecule. ) Tj 51.428571 0 0 51.428571 0 1118.6399 Tm 6.377778 0 Td 52.175926 Tz (Relocation ) Tj 3.402778 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 51.557239 Tz (carboxylate ) Tj 3.655556 0 Td 57.037037 Tz (group ) Tj 1.983333 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 60.185185 Tz (5564949 ) Tj 2.780556 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 1081.654367 Tm 6.358333 0 Td 60.925926 Tz (pound ) Tj 1.983333 0 Td 57.523148 Tz (from ) Tj 1.536111 0 Td 51.851852 Tz (the ) Tj 1.088889 0 Td 58.333333 Tz (meta ) Tj 1.536111 0 Td 46.990741 Tz (to ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 52.662037 Tz (para ) Tj 1.380556 0 Td 49.421296 Tz (position ) Tj 2.547222 0 Td 51.041667 Tz (Suggests ) Tj 2.605556 0 Td 45.37037 Tz (that ) Tj 1.225 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 53.472222 Tz (very ) Tj 51.428571 0 0 51.428571 0 1038.793264 Tm 6.358333 0 Td 46.450617 Tz (close, ) Tj 1.788889 0 Td 48.112536 Tz (energetically ) Tj 3.888889 0 Td 52.146465 Tz (unfavorable ) Tj 3.597222 0 Td 46.548822 Tz (interaction ) Tj 3.208333 0 Td 61.574074 Tz (would ) Tj 1.944444 0 Td 55.092593 Tz (occur ) Tj 1.75 0 Td 54.282407 Tz (with ) Tj 40 0 0 40 0 1006 Tm 8.15 0 Td 65.277778 Tz (the ) Tj 1.4 0 Td 75 Tz (backbone ) Tj 3.85 0 Td 70.833333 Tz (of ) Tj 1.025 0 Td 72.5 Tz (R284. ) Tj 2.4 0 Td 75.833333 Tz (These ) Tj 2.525 0 Td 73.611111 Tz (models ) Tj 2.9 0 Td 63.888889 Tz (are ) Tj 1.375 0 Td 62.5 Tz (consistent ) Tj 4 0 Td 67.708333 Tz (with ) Tj 1.875 0 Td 63.888889 Tz (the ) Tj 51.428571 0 0 51.428571 0 960.615187 Tm 6.358333 0 Td 49.259259 Tz (difference ) Tj 3.247222 0 Td 45.37037 Tz (in ) Tj 0.894444 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 43.981481 Tz (ability ) Tj 2.158333 0 Td 59.953704 Tz (of ) Tj 0.913889 0 Td 48.611111 Tz (the ) Tj 1.225 0 Td 60.185185 Tz (5564949 ) Tj 2.819444 0 Td 64.409722 Tz (compound ) Tj 3.383333 0 Td 55.740741 Tz (\(meta ) Tj 51.428571 0 0 51.428571 0 921.294118 Tm 6.358333 0 Td 53.240741 Tz (isomer\) ) Tj 2.411111 0 Td 58.333333 Tz (and ) Tj 1.263889 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 60.185185 Tz (5564676 ) Tj 2.741667 0 Td 63.599537 Tz (compound ) Tj 3.247222 0 Td 49.907407 Tz (\(para ) Tj 1.711111 0 Td 52.314815 Tz (isomer\) ) Tj 2.391667 0 Td 45.37037 Tz (to ) Tj 0.777778 0 Td 44.907407 Tz (inhibit ) Tj 38.571429 0 0 38.571429 0 887 Tm 8.503704 0 Td 86.419753 Tz (ATX. ) Tj 51.428571 0 0 51.428571 0 843.053763 Tm 7.097222 0 Td 62.654321 Tz (The ) Tj 1.380556 0 Td 41.319444 Tz (full ) Tj 1.244444 0 Td 51.851852 Tz (breadth ) Tj 2.430556 0 Td 58.333333 Tz (of ) Tj 0.875 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 45.37037 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.616667 0 Td 45.37037 Tz (that ) Tj 1.341667 0 Td 60.493827 Tz (met ) Tj 1.361111 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 805.404101 Tm 6.358333 0 Td 77.777778 Tz (ATX ) Tj 1.633333 0 Td 46.666667 Tz (inhibition ) Tj 3.013889 0 Td 52.391975 Tz (requirements ) Tj 3.966667 0 Td 53.703704 Tz (through ) Tj 2.488889 0 Td 42.939815 Tz (this ) Tj 1.283333 0 Td 55.902778 Tz (modeling ) Tj 2.897222 0 Td 51.851852 Tz (process ) Tj 51.428571 0 0 51.428571 0 763.674095 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 48.611111 Tz (further ) Tj 2.177778 0 Td 48.611111 Tz (analysis ) Tj 2.527778 0 Td 51.851852 Tz (were: ) Tj 110 0 0 110 0 507 Tm 7.027273 0 Td 43.939394 Tz (/ ) Tj 0.809091 0 Td 36.363636 Tz (\\ ) Tj 1.109091 0 Td 9.090909 Tz (. ) Tj 130.952381 0 0 130.952381 0 432.187755 Tm 4.368 0 Td 19.727273 Tz (\(, ) Tj 0.702545 0 Td 55.363636 Tz (X- ) Tj 0.748364 0 Td 35.636364 Tz ({ ) Tj 0.771273 0 Td 61.090909 Tz (} ) Tj 0.748364 0 Td 38.181818 Tz ({ ) Tj 1.741091 0 Td 26.727273 Tz (C ) Tj 31.428571 0 0 31.428571 0 224 Tm 23.036364 0 Td 76.515152 Tz (7905958 ) Tj 30 0 0 30 0 2755 Tm 41.833333 0 Td 72.222222 Tz (5 ) 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 40 0 0 40 0 2913 Tm 41.825 0 Td 66.666667 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2879 Tm 44.577273 0 Td 111.363636 Tz (OH ) Tj 21.445455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2849 Tm 55.3 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2833.776699 Tm 42.159091 0 Td 111.363636 Tz (O ) Tj 6.618182 0 Td 111.363636 Tz (O ) Tj 13.077273 0 Td 111.363636 Tz (O ) Tj 6.586364 0 Td 106.060606 Tz (OH ) Tj 234.285714 0 0 234.285714 0 2682 Tm 6.846341 0 Td 85.365854 Tz (oc. ) Tj 31.428571 0 0 31.428571 0 2660.223301 Tm 41.554545 0 Td 106.060606 Tz (HO ) Tj 7.222727 0 Td 111.363636 Tz (O ) Tj 13.077273 0 Td 111.363636 Tz (O ) Tj 6.586364 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 2615 Tm 44.577273 0 Td 111.363636 Tz (O ) Tj 20.840909 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2589 Tm 54.409091 0 Td 76.515152 Tz (5186522 ) Tj 106.428571 0 0 106.428571 0 2351.513699 Tm 18.256376 0 Td 32.885906 Tz (O ) Tj 0.732886 0 Td 195.749441 Tz (O ) Tj 31.428571 0 0 31.428571 0 2216 Tm 65.513636 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2186 Tm 61.409091 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 1782 Tm 54.027273 0 Td 76.515152 Tz (7839888 ) Tj 32.857143 0 0 32.857143 0 1638 Tm 63.152174 0 Td 91.304348 Tz (O ) Tj 31.428571 0 0 31.428571 0 1594 Tm 68.472727 0 Td 111.363636 Tz (OH ) Tj 31.428571 0 0 31.428571 0 1508.333333 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 6.554545 0 Td 111.363636 Tz (O ) Tj 6.554545 0 Td 111.363636 Tz (O ) Tj 232.857143 0 0 232.857143 0 1353 Tm 6.892638 0 Td 51.390593 Tz (cric: ) Tj 31.428571 0 0 31.428571 0 1333 Tm 48.745455 0 Td 111.363636 Tz (O ) Tj 13.109091 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1242 Tm 41.554545 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 1198 Tm 44.577273 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1160 Tm 54.027273 0 Td 75.757576 Tz (5761473 ) Tj 79.52381 0 0 79.52381 0 923.201342 Tm 19.239521 0 Td 44.011976 Tz (O ) Tj 5.608383 0 Td 48.203593 Tz (N ) Tj 1.408383 0 Td 220.05988 Tz (O ) Tj 31.428571 0 0 31.428571 0 850 Tm 46.518182 0 Td 106.060606 Tz (HN ) Tj 31.428571 0 0 31.428571 0 821 Tm 56.413636 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 709.540984 Tm 41.618182 0 Td 106.060606 Tz (HO ) Tj 14.636364 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 615 Tm 43.845455 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 578 Tm 54.027273 0 Td 76.515152 Tz (5564949 ) Tj 31.428571 0 0 31.428571 0 372 Tm 41.522727 0 Td 121.969697 Tz (N ) Tj 31.428571 0 0 31.428571 0 351 Tm 63.509091 0 Td 106.060606 Tz (H ) Tj 31.428571 0 0 31.428571 0 306 Tm 47.186364 0 Td 106.060606 Tz (H ) Tj 34.285714 0 0 34.285714 0 243 Tm 44.770833 0 Td 102.083333 Tz (O ) Tj 11.8125 0 Td 102.083333 Tz (O ) Tj 1.575 0 Td 102.083333 Tz (O ) Tj 31.428571 0 0 31.428571 0 215 Tm 54.377273 0 Td 77.272727 Tz (5538444 ) Tj 1.428571 0 0 1.428571 0 2186 Tm 941.5 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 112 0 obj << /Length 1 >> stream q endstream endobj 113 0 obj << /Length 37765 >> 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 57.154882 Tz (8,268,891 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 52.857143 0 0 52.857143 0 2968 Tm 14.472973 0 Td 72.522523 Tz (9 ) Tj 40 0 0 40 0 2913 Tm 17.475 0 Td 67.083333 Tz (-continued ) Tj 31.428571 0 0 31.428571 0 2836 Tm 37.290909 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 2572 Tm 11.2 0 Td 106.060606 Tz (HO ) Tj 31.428571 0 0 31.428571 0 2494 Tm 22.240909 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 2435 Tm 23.036364 0 Td 72.474747 Tz (571 ) Tj 1.463636 0 Td 71.590909 Tz (1925 ) Tj 305.714286 0 0 305.714286 0 2030 Tm 2.028037 0 Td 80.412773 Tz (rico ) Tj 31.428571 0 0 31.428571 0 1993 Tm 23.036364 0 Td 66.287879 Tz (79.21385 ) Tj 31.428571 0 0 31.428571 0 1953 Tm 25.804545 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1953 Tm 12.313636 0 Td 111.363636 Tz (OH ) Tj 220.952381 0 0 220.952381 0 1779.707317 Tm 1.575 0 Td 30.172414 Tz (- ) Tj 0.429957 0 Td 76.185345 Tz (C ) Tj 0.99569 0 Td 79.202586 Tz (O ) Tj 31.428571 0 0 31.428571 0 1770 Tm 19.059091 0 Td 95.454545 Tz (O ) Tj 31.428571 0 0 31.428571 0 1517 Tm 23.036364 0 Td 77.272727 Tz (5210574 ) Tj 51.428571 0 0 51.428571 0 1398.790427 Tm 7.097222 0 Td 66.435185 Tz (As ) Tj 1.030556 0 Td 51.851852 Tz (alluded ) Tj 2.411111 0 Td 46.990741 Tz (to ) Tj 0.836111 0 Td 52.391975 Tz (above, ) Tj 2.138889 0 Td 50.555556 Tz (these ) Tj 1.730556 0 Td 62.294239 Tz (compounds ) Tj 3.636111 0 Td 59.953704 Tz (were ) Tj 1.691667 0 Td 54.768519 Tz (determined ) Tj 51.428571 0 0 51.428571 0 1359.172781 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.469444 0 Td 55.555556 Tz (docking ) Tj 2.508333 0 Td 47.685185 Tz (studies ) Tj 2.197222 0 Td 58.333333 Tz (which ) Tj 1.925 0 Td 48.341049 Tz (additionally ) Tj 3.636111 0 Td 54.282407 Tz (provided ) Tj 2.780556 0 Td 47.222222 Tz (insight ) Tj 51.428571 0 0 51.428571 0 1311.597156 Tm 6.358333 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 52.824074 Tz (unforeseen ) Tj 3.325 0 Td 52.777778 Tz (binding ) Tj 2.391667 0 Td 56.17284 Tz (modes. ) Tj 2.158333 0 Td 63.734568 Tz (The ) Tj 1.302778 0 Td 59.722222 Tz (7839888 ) Tj 2.644444 0 Td 64.814815 Tz (compound ) Tj 3.247222 0 Td 61.574074 Tz (was ) Tj 40 0 0 40 0 1274 Tm 8.2 0 Td 62.5 Tz (selected ) Tj 3.3 0 Td 62.5 Tz (for ) Tj 1.4 0 Td 58.333333 Tz (in ) Tj 1.025 0 Td 55.555556 Tz (silico ) Tj 2.325 0 Td 63.75 Tz (evaluation ) Tj 4.15 0 Td 77.083333 Tz (on ) Tj 1.25 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 62.5 Tz (basis ) Tj 2.225 0 Td 70.833333 Tz (of ) Tj 1.075 0 Td 62.5 Tz (the ) Tj 1.45 0 Td 77.777778 Tz (oxocar ) Tj 51.428571 0 0 51.428571 0 1225.603513 Tm 6.338889 0 Td 52.662037 Tz (boxylate ) Tj 2.8 0 Td 48.935185 Tz (functional ) Tj 3.208333 0 Td 52.391975 Tz (group, ) Tj 2.177778 0 Td 58.333333 Tz (which ) Tj 2.041667 0 Td 61.574074 Tz (was ) Tj 1.4 0 Td 53.472222 Tz (expected ) Tj 2.838889 0 Td 45.37037 Tz (to ) Tj 0.855556 0 Td 45.37037 Tz (interact ) Tj 51.428571 0 0 51.428571 0 1180.401242 Tm 6.358333 0 Td 50.771605 Tz (favorably ) Tj 2.955556 0 Td 53.472222 Tz (with ) Tj 1.497222 0 Td 48.611111 Tz (the ) Tj 1.05 0 Td 48.070988 Tz (active ) Tj 1.925 0 Td 42.12963 Tz (site ) Tj 1.225 0 Td 53.148148 Tz (metal ) Tj 1.808333 0 Td 45.37037 Tz (ions. ) Tj 1.536111 0 Td 64.814815 Tz (The ) Tj 1.380556 0 Td 49.016204 Tz (thiourea ) Tj 2.547222 0 Td 64.00463 Tz (func ) Tj 51.428571 0 0 51.428571 0 1138.203956 Tm 6.338889 0 Td 46.450617 Tz (tional ) Tj 1.827778 0 Td 57.037037 Tz (group ) Tj 1.925 0 Td 55.092593 Tz (of ) Tj 0.758333 0 Td 43.75 Tz (this ) Tj 1.225 0 Td 63.599537 Tz (compound ) Tj 3.266667 0 Td 62.654321 Tz (was ) Tj 1.302778 0 Td 56.388889 Tz (found ) Tj 1.866667 0 Td 45.37037 Tz (to ) Tj 0.758333 0 Td 50.462963 Tz (involve ) Tj 2.275 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 51.203704 Tz (ligat ) Tj 51.428571 0 0 51.428571 0 1091.471769 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.127778 0 Td 57.253086 Tz (one ) Tj 1.205556 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 48.070988 Tz (active ) Tj 1.925 0 Td 41.319444 Tz (site ) Tj 1.186111 0 Td 52.5 Tz (metal ) Tj 1.788889 0 Td 44.722222 Tz (ions. ) Tj 1.536111 0 Td 53.472222 Tz (This ) Tj 1.497222 0 Td 46.548822 Tz (interaction ) Tj 3.266667 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1050.468085 Tm 6.358333 0 Td 44.871795 Tz (electrostatic ) Tj 3.713889 0 Td 46.720679 Tz (interactions ) Tj 3.538889 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 51.262626 Tz (carboxylate ) Tj 3.597222 0 Td 48.611111 Tz (functional ) Tj 3.091667 0 Td 56.388889 Tz (group ) Tj 51.428571 0 0 51.428571 0 1006.542714 Tm 6.338889 0 Td 54.282407 Tz (with ) Tj 1.516667 0 Td 60.763889 Tz (8284 ) Tj 1.691667 0 Td 58.333333 Tz (and ) Tj 1.302778 0 Td 64.814815 Tz (K249 ) Tj 1.769444 0 Td 50.771605 Tz (are ) Tj 1.127778 0 Td 45.37037 Tz (likely ) Tj 1.886111 0 Td 49.789562 Tz (responsible ) Tj 3.519444 0 Td 48.611111 Tz (for ) Tj 1.069444 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 46.450617 Tz (resultant ) Tj 51.428571 0 0 51.428571 0 961.693069 Tm 6.377778 0 Td 72.376543 Tz (59% ) Tj 1.516667 0 Td 77.777778 Tz (ATX ) Tj 1.691667 0 Td 46.666667 Tz (inhibition ) Tj 3.052778 0 Td 51.49177 Tz (observed. ) Tj 3.013889 0 Td 64.814815 Tz (The ) Tj 1.4 0 Td 51.203704 Tz (other ) Tj 1.75 0 Td 61.574074 Tz (compounds ) Tj 3.636111 0 Td 58.333333 Tz (were ) Tj 48.571429 0 0 48.571429 0 919 Tm 6.732353 0 Td 60.392157 Tz (found ) Tj 2.038235 0 Td 48.039216 Tz (to ) Tj 0.864706 0 Td 61.764706 Tz (meet ) Tj 1.729412 0 Td 51.470588 Tz (the ) Tj 1.173529 0 Td 52.941176 Tz (desired ) Tj 2.408824 0 Td 83.496732 Tz (ATX ) Tj 1.75 0 Td 49.754902 Tz (inhibition ) Tj 3.232353 0 Td 48.611111 Tz (levels ) Tj 2.017647 0 Td 51.470588 Tz (as ) Tj 0.905882 0 Td 49.411765 Tz (well, ) Tj 1.708824 0 Td 54.901961 Tz (as ) Tj 51.428571 0 0 51.428571 0 879.96861 Tm 6.358333 0 Td 53.877315 Tz (provided ) Tj 2.761111 0 Td 45.37037 Tz (in ) Tj 0.758333 0 Td 48.611111 Tz (the ) Tj 1.108333 0 Td 58.333333 Tz (Examples ) Tj 2.994444 0 Td 51.851852 Tz (below. ) Tj 51.428571 0 0 51.428571 0 837.056628 Tm 7.116667 0 Td 50.87963 Tz (Previously ) Tj 3.325 0 Td 49.826389 Tz (reported ) Tj 2.566667 0 Td 77.777778 Tz (ATX ) Tj 1.613889 0 Td 46.342593 Tz (inhibitors ) Tj 2.994444 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 41.049383 Tz (all ) Tj 0.952778 0 Td 52.777778 Tz (analogs ) Tj 2.411111 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 795.506053 Tm 6.358333 0 Td 45.37037 Tz (catalytic ) Tj 2.605556 0 Td 50.231481 Tz (product, ) Tj 2.605556 0 Td 60.763889 Tz (LPA, ) Tj 1.594444 0 Td 60.493827 Tz (and ) Tj 1.225 0 Td 40.509259 Tz (fail ) Tj 1.108333 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 59.143519 Tz (meet ) Tj 1.575 0 Td 58.333333 Tz (most ) Tj 1.575 0 Td 50.462963 Tz (metrics ) Tj 2.275 0 Td 51.851852 Tz (applied ) Tj 51.428571 0 0 51.428571 0 752.014458 Tm 6.338889 0 Td 46.990741 Tz (to ) Tj 0.758333 0 Td 54.012346 Tz (determine ) Tj 3.091667 0 Td 48.37963 Tz (drug-likeness. ) Tj 4.219444 0 Td 64.814815 Tz (The ) Tj 1.341667 0 Td 59.143519 Tz (most ) Tj 1.575 0 Td 70.216049 Tz (common ) Tj 2.741667 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.907407 Tz (these ) Tj 1.691667 0 Td 72.376543 Tz (met ) Tj 51.428571 0 0 51.428571 0 710.503759 Tm 6.358333 0 Td 43.75 Tz (rics ) Tj 1.225 0 Td 50.771605 Tz (are ) Tj 1.108333 0 Td 48.611111 Tz (Lipinskis ) Tj 3.15 0 Td 42.669753 Tz (rules. ) Tj 1.730556 0 Td 58.333333 Tz (These ) Tj 1.983333 0 Td 45.37037 Tz (rules ) Tj 1.536111 0 Td 50.771605 Tz (are ) Tj 1.069444 0 Td 56.388889 Tz (based ) Tj 1.866667 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 59.62963 Tz (obser ) Tj 51.428571 0 0 51.428571 0 670.371362 Tm 6.358333 0 Td 49.691358 Tz (vation ) Tj 1.905556 0 Td 46.180556 Tz (that ) Tj 1.186111 0 Td 57.523148 Tz (poor ) Tj 1.458333 0 Td 48.611111 Tz (biological ) Tj 3.052778 0 Td 46.180556 Tz (distribution ) Tj 3.422222 0 Td 52.391975 Tz (occurs ) Tj 2.022222 0 Td 64.814815 Tz (when ) Tj 1.691667 0 Td 45.694444 Tz (solubility ) Tj 51.428571 0 0 51.428571 0 627.928205 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.380556 0 Td 50.771605 Tz (permeability ) Tj 4.005556 0 Td 49.691358 Tz (are ) Tj 1.225 0 Td 54.62963 Tz (reduced ) Tj 2.625 0 Td 58.333333 Tz (due ) Tj 1.361111 0 Td 45.37037 Tz (to ) Tj 0.875 0 Td 51.131687 Tz (excessive ) Tj 3.111111 0 Td 54.012346 Tz (molecular ) Tj 51.428571 0 0 51.428571 0 587.133005 Tm 6.338889 0 Td 56.17284 Tz (weight ) Tj 2.236111 0 Td 56.018519 Tz (\(2500\), ) Tj 2.586111 0 Td 48.611111 Tz (large ) Tj 1.691667 0 Td 57.87037 Tz (numbers ) Tj 2.683333 0 Td 59.953704 Tz (of ) Tj 0.836111 0 Td 56.30787 Tz (hydrogen ) Tj 2.936111 0 Td 62.384259 Tz (bond ) Tj 1.711111 0 Td 54.552469 Tz (donors ) Tj 2.197222 0 Td 53.472222 Tz (or ) Tj 51.428571 0 0 51.428571 0 545.979487 Tm 6.358333 0 Td 50.771605 Tz (acceptors ) Tj 3.033333 0 Td 65.895062 Tz (\(25 ) Tj 1.477778 0 Td 50.231481 Tz (or ) Tj 0.894444 0 Td 61.574074 Tz (210, ) Tj 1.769444 0 Td 46.296296 Tz (respectively\), ) Tj 4.161111 0 Td 58.333333 Tz (and ) Tj 1.322222 0 Td 48.935185 Tz (calculated ) Tj 3.227778 0 Td 50.771605 Tz (log ) Tj 1.205556 0 Td 61.574074 Tz (P ) Tj 51.428571 0 0 51.428571 0 503.724221 Tm 6.377778 0 Td 53.148148 Tz (\(25\). ) Tj 1.769444 0 Td 50.925926 Tz (Several ) Tj 2.294444 0 Td 50.87963 Tz (extensions ) Tj 3.169444 0 Td 48.611111 Tz (to ) Tj 0.777778 0 Td 47.962963 Tz (Lipinski's ) Tj 3.072222 0 Td 46.018519 Tz (rules ) Tj 1.536111 0 Td 56.712963 Tz (have ) Tj 1.477778 0 Td 55.092593 Tz (appeared ) Tj 2.8 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 461.97 Tm 6.338889 0 Td 50.771605 Tz (the ) Tj 1.127778 0 Td 41.540404 Tz (literature. ) Tj 3.033333 0 Td 34.027778 Tz (It ) Tj 0.602778 0 Td 52.932099 Tz (has ) Tj 1.166667 0 Td 56.712963 Tz (been ) Tj 1.575 0 Td 56.388889 Tz (found ) Tj 1.905556 0 Td 45.37037 Tz (that ) Tj 1.283333 0 Td 49.583333 Tz (increasing ) Tj 3.169444 0 Td 42.424242 Tz (flexibility ) Tj 2.994444 0 Td 51.851852 Tz (as ) Tj 51.428571 0 0 51.428571 0 419.480048 Tm 6.358333 0 Td 46.450617 Tz (reflected ) Tj 2.702778 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 56.712963 Tz (an ) Tj 0.894444 0 Td 49.583333 Tz (increasing ) Tj 3.188889 0 Td 61.574074 Tz (number ) Tj 2.352778 0 Td 58.333333 Tz (of ) Tj 0.797222 0 Td 46.8107 Tz (rotatable ) Tj 2.702778 0 Td 57.685185 Tz (bonds ) Tj 1.925 0 Td 52.314815 Tz (reduces ) Tj 51.428571 0 0 51.428571 0 379.866831 Tm 6.358333 0 Td 46.990741 Tz (oral ) Tj 1.361111 0 Td 44.357639 Tz (bioavailability. ) Tj 4.569444 0 Td 58.333333 Tz (Nine ) Tj 1.613889 0 Td 62.294239 Tz (compounds ) Tj 3.616667 0 Td 58.333333 Tz (were ) Tj 1.633333 0 Td 46.018519 Tz (identified ) Tj 2.975 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 340.607565 Tm 6.358333 0 Td 49.537037 Tz (current ) Tj 2.197222 0 Td 52.5 Tz (study ) Tj 1.711111 0 Td 50.231481 Tz (as ) Tj 0.777778 0 Td 53.06713 Tz (reducing ) Tj 2.683333 0 Td 48.611111 Tz (the ) Tj 0.972222 0 Td 56.339031 Tz (ATX-catalyzed ) Tj 4.569444 0 Td 56.712963 Tz (FS-3 ) Tj 1.536111 0 Td 50.231481 Tz (hydrolysis ) Tj 51.428571 0 0 51.428571 0 295.082192 Tm 6.338889 0 Td 61.574074 Tz (by ) Tj 0.894444 0 Td 72.376543 Tz (50% ) Tj 1.419444 0 Td 53.472222 Tz (or ) Tj 0.758333 0 Td 63.194444 Tz (more ) Tj 1.613889 0 Td 42.12963 Tz (at ) Tj 0.719444 0 Td 55.092593 Tz (10 ) Tj 1.147222 0 Td 68.055556 Tz (M. ) Tj 0.894444 0 Td 71.296296 Tz (Two ) Tj 1.4 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 49.259259 Tz (these ) Tj 1.613889 0 Td 61.574074 Tz (compounds ) Tj 3.480556 0 Td 51.851852 Tz (\(571 ) Tj 1.341667 0 Td 58.333333 Tz (1925 ) Tj 51.428571 0 0 51.428571 0 254.871275 Tm 6.358333 0 Td 58.333333 Tz (and ) Tj 1.205556 0 Td 56.712963 Tz (7921385, ) Tj 2.858333 0 Td 51.851852 Tz (presented ) Tj 2.955556 0 Td 54.552469 Tz (above\) ) Tj 2.1 0 Td 59.953704 Tz (comply ) Tj 2.352778 0 Td 52.662037 Tz (with ) Tj 1.419444 0 Td 39.969136 Tz (all ) Tj 0.855556 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 48.935185 Tz (Lipinski's ) Tj 48.571429 0 0 48.571429 0 212 Tm 6.732353 0 Td 49.411765 Tz (rules ) Tj 1.647059 0 Td 62.908497 Tz (and ) Tj 1.276471 0 Td 60.04902 Tz (have ) Tj 1.626471 0 Td 58.333333 Tz (fewer ) Tj 1.894118 0 Td 54.044118 Tz (than ) Tj 1.523529 0 Td 60.04902 Tz (10 ) Tj 0.885294 0 Td 49.945534 Tz (rotatable ) Tj 2.841176 0 Td 56.617647 Tz (bonds, ) Tj 2.223529 0 Td 52.328431 Tz (thus ) Tj 1.4 0 Td 52.328431 Tz (also ) Tj 1.441176 0 Td 72.058824 Tz (meet ) Tj 51.428571 0 0 51.428571 0 170.005222 Tm 6.358333 0 Td 51.851852 Tz (ing ) Tj 1.302778 0 Td 48.611111 Tz (the ) Tj 1.205556 0 Td 55.497685 Tz (extended ) Tj 2.994444 0 Td 42.424242 Tz (flexibility ) Tj 3.227778 0 Td 47.222222 Tz (metric. ) Tj 2.391667 0 Td 51.041667 Tz (Five ) Tj 1.575 0 Td 48.287037 Tz (additional ) Tj 3.247222 0 Td 84.259259 Tz (com ) 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 32.672973 0 Td 74.099099 Tz (10 ) Tj 51.428571 0 0 51.428571 0 2914.19337 Tm 25.277778 0 Td 58.333333 Tz (pounds ) Tj 2.780556 0 Td 55.092593 Tz (\(7839888, ) Tj 3.655556 0 Td 56.30787 Tz (5186522, ) Tj 3.402778 0 Td 56.30787 Tz (5761473, ) Tj 3.402778 0 Td 60.185185 Tz (5538444 ) Tj 3.188889 0 Td 59.41358 Tz (and ) Tj 51.428571 0 0 51.428571 0 2872.002442 Tm 25.297222 0 Td 56.712963 Tz (7905958, ) Tj 2.936111 0 Td 54.552469 Tz (above\) ) Tj 2.119444 0 Td 56.712963 Tz (exceed ) Tj 2.216667 0 Td 54.282407 Tz (only ) Tj 1.516667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 54.012346 Tz (molecular ) Tj 3.111111 0 Td 54.012346 Tz (weight ) Tj 2.158333 0 Td 46.666667 Tz (limit ) Tj 1.555556 0 Td 61.574074 Tz (by ) Tj 51.428571 0 0 51.428571 0 2827.151515 Tm 25.297222 0 Td 58.333333 Tz (amounts ) Tj 2.722222 0 Td 52.777778 Tz (ranging ) Tj 2.45 0 Td 57.523148 Tz (from ) Tj 1.652778 0 Td 55.092593 Tz (7 ) Tj 0.583333 0 Td 55.812757 Tz (\(7905958\) ) Tj 3.266667 0 Td 45.37037 Tz (to ) Tj 0.855556 0 Td 58.333333 Tz (148 ) Tj 1.263889 0 Td 53.472222 Tz (\(5186522\). ) Tj 3.461111 0 Td 66.975309 Tz (One ) Tj 51.428571 0 0 51.428571 0 2786.656899 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 56.532922 Tz (\(5564949\) ) Tj 3.208333 0 Td 55.555556 Tz (exceeds ) Tj 2.488889 0 Td 54.282407 Tz (only ) Tj 1.536111 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 49.259259 Tz (calculated ) Tj 3.169444 0 Td 50.771605 Tz (log ) Tj 1.147222 0 Td 64.814815 Tz (P ) Tj 0.544444 0 Td 57.253086 Tz (cri ) Tj 51.428571 0 0 51.428571 0 2744.531707 Tm 25.277778 0 Td 44.444444 Tz (terion. ) Tj 2.1 0 Td 62.654321 Tz (The ) Tj 1.322222 0 Td 43.425926 Tz (final ) Tj 1.516667 0 Td 63.599537 Tz (compound ) Tj 3.266667 0 Td 56.532922 Tz (\(5210574\) ) Tj 3.247222 0 Td 54.166667 Tz (exceeds ) Tj 2.508333 0 Td 58.333333 Tz (two ) Tj 1.283333 0 Td 41.049383 Tz (criteria, ) Tj 51.428571 0 0 51.428571 0 2702.622739 Tm 25.297222 0 Td 49.259259 Tz (calculated ) Tj 3.247222 0 Td 50.771605 Tz (log ) Tj 1.225 0 Td 64.814815 Tz (P ) Tj 0.641667 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 54.012346 Tz (molecular ) Tj 3.169444 0 Td 50.925926 Tz (weight. ) Tj 2.469444 0 Td 64.814815 Tz (None ) Tj 1.808333 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.147222 0 Td 84.259259 Tz (com ) Tj 51.428571 0 0 51.428571 0 2661.032569 Tm 25.297222 0 Td 57.79321 Tz (pounds ) Tj 2.294444 0 Td 48.206019 Tz (violated ) Tj 2.508333 0 Td 48.611111 Tz (the ) Tj 1.069444 0 Td 61.868687 Tz (recommended ) Tj 4.258333 0 Td 45.37037 Tz (limits ) Tj 1.808333 0 Td 59.953704 Tz (on ) Tj 0.933333 0 Td 46.450617 Tz (rotatable ) Tj 2.663889 0 Td 52.932099 Tz (bonds, ) Tj 51.428571 0 0 51.428571 0 2622.103774 Tm 25.277778 0 Td 57.118056 Tz (hydrogen ) Tj 2.877778 0 Td 61.574074 Tz (bond ) Tj 1.575 0 Td 49.259259 Tz (acceptors, ) Tj 3.091667 0 Td 51.851852 Tz (or ) Tj 0.719444 0 Td 57.523148 Tz (hydrogen ) Tj 2.877778 0 Td 60.763889 Tz (bond ) Tj 1.594444 0 Td 50.925926 Tz (donors. ) Tj 2.275 0 Td 59.953704 Tz (Thus ) Tj 1.575 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 2581.336774 Tm 25.297222 0 Td 51.851852 Tz (goal ) Tj 1.497222 0 Td 58.333333 Tz (of ) Tj 0.855556 0 Td 53.347578 Tz (demonstrating ) Tj 4.394444 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 78.858025 Tz (ATX ) Tj 1.691667 0 Td 37.268519 Tz (is ) Tj 0.7 0 Td 58.333333 Tz (a ) Tj 0.797222 0 Td 55.092593 Tz (druggable ) Tj 3.344444 0 Td 46.450617 Tz (target ) Tj 1.886111 0 Td 55.092593 Tz (has ) Tj 51.428571 0 0 51.428571 0 2536.895288 Tm 25.277778 0 Td 57.523148 Tz (been ) Tj 1.672222 0 Td 53.472222 Tz (achieved ) Tj 2.877778 0 Td 43.75 Tz (in ) Tj 0.836111 0 Td 53.148148 Tz (terms ) Tj 1.905556 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 49.907407 Tz (these ) Tj 1.827778 0 Td 50.231481 Tz (nine ) Tj 1.497222 0 Td 58.657407 Tz (compounds, ) Tj 3.830556 0 Td 43.75 Tz (at ) Tj 0.816667 0 Td 44.722222 Tz (least ) Tj 51.428571 0 0 51.428571 0 2496.87309 Tm 25.297222 0 Td 50.05144 Tz (exhibited ) Tj 2.8 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 51.131687 Tz (necessary ) Tj 2.916667 0 Td 44.444444 Tz (results ) Tj 2.002778 0 Td 56.388889 Tz (under ) Tj 1.788889 0 Td 48.611111 Tz (Lipinskis ) Tj 3.091667 0 Td 45.37037 Tz (rules ) Tj 1.477778 0 Td 55.555556 Tz (coupled ) Tj 51.428571 0 0 51.428571 0 2454.859903 Tm 25.277778 0 Td 54.282407 Tz (with ) Tj 1.477778 0 Td 46.450617 Tz (effective ) Tj 2.625 0 Td 78.858025 Tz (ATX ) Tj 1.575 0 Td 46.990741 Tz (inhibition ) Tj 2.994444 0 Td 46.450617 Tz (\(as ) Tj 1.030556 0 Td 51.49177 Tz (presented ) Tj 2.936111 0 Td 46.990741 Tz (in ) Tj 0.738889 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 55.092593 Tz (Examples, ) Tj 51.428571 0 0 51.428571 0 2410 Tm 25.277778 0 Td 51.851852 Tz (below\). ) Tj 51.428571 0 0 51.428571 0 2372.830552 Tm 26.016667 0 Td 66.435185 Tz (AS ) Tj 0.991667 0 Td 49.259259 Tz (Such, ) Tj 1.672222 0 Td 50.555556 Tz (these ) Tj 1.672222 0 Td 61.934156 Tz (compounds ) Tj 3.558333 0 Td 66.975309 Tz (may ) Tj 1.380556 0 Td 58.333333 Tz (be ) Tj 0.855556 0 Td 52.256944 Tz (included ) Tj 2.683333 0 Td 45.37037 Tz (in ) Tj 0.7 0 Td 58.333333 Tz (a ) Tj 0.525 0 Td 64.351852 Tz (composi ) Tj 51.428571 0 0 51.428571 0 2332.575448 Tm 25.277778 0 Td 46.990741 Tz (tion ) Tj 1.361111 0 Td 56.712963 Tz (of ) Tj 0.777778 0 Td 57.253086 Tz (any ) Tj 1.205556 0 Td 53.472222 Tz (type ) Tj 1.477778 0 Td 46.180556 Tz (that ) Tj 1.302778 0 Td 37.268519 Tz (is ) Tj 0.622222 0 Td 51.446759 Tz (properly ) Tj 2.683333 0 Td 49.259259 Tz (ingestable ) Tj 3.130556 0 Td 59.953704 Tz (by ) Tj 0.933333 0 Td 55.092593 Tz (a ) Tj 0.505556 0 Td 44.560185 Tz (patient. ) Tj 2.391667 0 Td 35.648148 Tz (It ) Tj 0.602778 0 Td 40.509259 Tz (is ) Tj 51.428571 0 0 51.428571 0 2290.940594 Tm 25.297222 0 Td 49.259259 Tz (preferable ) Tj 3.227778 0 Td 44.560185 Tz (that ) Tj 1.322222 0 Td 55.092593 Tz (such ) Tj 1.575 0 Td 54.012346 Tz (compositions ) Tj 4.122222 0 Td 59.953704 Tz (be ) Tj 0.952778 0 Td 47.530864 Tz (orally ) Tj 1.983333 0 Td 47.138047 Tz (ingestable, ) Tj 3.363889 0 Td 51.851852 Tz (but ) Tj 51.428571 0 0 51.428571 0 2246.599749 Tm 25.277778 0 Td 51.851852 Tz (they ) Tj 1.477778 0 Td 66.975309 Tz (may ) Tj 1.4 0 Td 56.712963 Tz (be ) Tj 0.855556 0 Td 53.877315 Tz (provided ) Tj 2.780556 0 Td 48.611111 Tz (for ) Tj 1.011111 0 Td 50.968013 Tz (intravenous ) Tj 3.577778 0 Td 48.881173 Tz (introduction ) Tj 3.694444 0 Td 51.851852 Tz (as ) Tj 0.816667 0 Td 46.666667 Tz (well. ) Tj 51.428571 0 0 51.428571 0 2205.515994 Tm 26.036111 0 Td 48.611111 Tz (In ) Tj 0.894444 0 Td 53.796296 Tz (terms ) Tj 1.925 0 Td 56.712963 Tz (of ) Tj 0.894444 0 Td 49.691358 Tz (the ) Tj 1.205556 0 Td 57.523148 Tz (form ) Tj 1.730556 0 Td 54.282407 Tz (Such ) Tj 1.613889 0 Td 53.742284 Tz (compositions ) Tj 4.2 0 Td 68.055556 Tz (may ) Tj 1.536111 0 Td 46.018519 Tz (take, ) Tj 1.672222 0 Td 58.333333 Tz (any ) Tj 51.428571 0 0 51.428571 0 2164.588875 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 2122.34 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 2079.218863 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 Tz (the ) Tj 1.05 0 Td 40.185185 Tz (like. ) Tj 1.419444 0 Td 42.12963 Tz (If ) Tj 0.583333 0 Td 48.611111 Tz (in ) Tj 51.428571 0 0 51.428571 0 2038.613267 Tm 25.297222 0 Td 52.932099 Tz (coated ) Tj 2.138889 0 Td 44.830247 Tz (tablet ) Tj 1.866667 0 Td 52.5 Tz (form, ) Tj 1.827778 0 Td 54.282407 Tz (such ) Tj 1.575 0 Td 53.472222 Tz (compositions ) Tj 4.122222 0 Td 68.055556 Tz (may ) Tj 1.458333 0 Td 58.333333 Tz (be ) Tj 0.952778 0 Td 55.092593 Tz (of ) Tj 0.836111 0 Td 50.05144 Tz (Sustained ) Tj 51.428571 0 0 51.428571 0 1996.741259 Tm 25.297222 0 Td 48.148148 Tz (release ) Tj 2.138889 0 Td 47.314815 Tz (type, ) Tj 1.536111 0 Td 59.41358 Tz (and ) Tj 1.186111 0 Td 68.055556 Tz (may ) Tj 1.341667 0 Td 53.472222 Tz (includea ) Tj 2.722222 0 Td 52.083333 Tz (waterinsoluble ) Tj 4.472222 0 Td 51.851852 Tz (but ) Tj 1.011111 0 Td 56.893004 Tz (permeable ) Tj 51.428571 0 0 51.428571 0 1957.842384 Tm 25.297222 0 Td 47.800926 Tz (film ) Tj 1.516667 0 Td 51.388889 Tz (coating ) Tj 2.527778 0 Td 53.030303 Tz (Surrounding ) Tj 3.85 0 Td 55.092593 Tz (a ) Tj 0.661111 0 Td 52.662037 Tz (core ) Tj 1.594444 0 Td 45.910494 Tz (tablet ) Tj 1.983333 0 Td 58.333333 Tz (and ) Tj 1.380556 0 Td 58.333333 Tz (a ) Tj 0.7 0 Td 44.830247 Tz (particulate, ) Tj 51.428571 0 0 51.428571 0 1914.357055 Tm 25.277778 0 Td 49.074074 Tz (water-soluble, ) Tj 4.433333 0 Td 54.282407 Tz (pore-forming ) Tj 4.258333 0 Td 48.611111 Tz (material ) Tj 2.683333 0 Td 50.771605 Tz (dispersed ) Tj 3.052778 0 Td 50.771605 Tz (within ) Tj 2.158333 0 Td 50.771605 Tz (the ) Tj 51.428571 0 0 51.428571 0 1874.527578 Tm 25.297222 0 Td 47.800926 Tz (film ) Tj 1.283333 0 Td 48.206019 Tz (coating. ) Tj 2.469444 0 Td 59.143519 Tz (Such ) Tj 1.555556 0 Td 51.851852 Tz (a ) Tj 0.447222 0 Td 55.092593 Tz (system ) Tj 2.138889 0 Td 50.231481 Tz (thus ) Tj 1.341667 0 Td 51.446759 Tz (provides ) Tj 2.605556 0 Td 56.712963 Tz (an ) Tj 0.836111 0 Td 54.166667 Tz (osmotic ) Tj 2.391667 0 Td 50.231481 Tz (gradient ) Tj 51.428571 0 0 51.428571 0 1832.46356 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 53.703704 Tz (channel ) Tj 2.430556 0 Td 55.555556 Tz (forming ) Tj 2.508333 0 Td 51.851852 Tz (system. ) Tj 2.352778 0 Td 51.388889 Tz (Typical ) Tj 2.352778 0 Td 50.231481 Tz (coatings ) Tj 2.566667 0 Td 56.712963 Tz (have ) Tj 1.516667 0 Td 52.662037 Tz (included ) Tj 51.428571 0 0 51.428571 0 1792.270809 Tm 25.297222 0 Td 54.6875 Tz (carnauba ) Tj 2.780556 0 Td 57.523148 Tz (wax, ) Tj 1.555556 0 Td 49.016204 Tz (cysteine ) Tj 2.527778 0 Td 50.694444 Tz (hydrochloride, ) Tj 4.413889 0 Td 55.34188 Tz (hydroxypropyl ) Tj 4.530556 0 Td 68.865741 Tz (meth ) Tj 51.428571 0 0 51.428571 0 1750.522459 Tm 25.277778 0 Td 46.450617 Tz (ylcellulose, ) Tj 3.597222 0 Td 61.213992 Tz (magnesium ) Tj 3.577778 0 Td 43.930041 Tz (Stearate, ) Tj 2.625 0 Td 49.016204 Tz (microcrystalline ) Tj 4.938889 0 Td 45.37037 Tz (cellulose, ) Tj 51.428571 0 0 51.428571 0 1707.320958 Tm 25.297222 0 Td 52.121914 Tz (polyethylene ) Tj 3.927778 0 Td 50.231481 Tz (glycol ) Tj 2.022222 0 Td 59.41358 Tz (and ) Tj 1.263889 0 Td 49.826389 Tz (titanium ) Tj 2.625 0 Td 48.206019 Tz (dioxide. ) Tj 2.547222 0 Td 56.388889 Tz (Other ) Tj 1.866667 0 Td 48.611111 Tz (therapeutic ) Tj 51.428571 0 0 51.428571 0 1664.474328 Tm 25.297222 0 Td 51.311728 Tz (agents ) Tj 2.041667 0 Td 68.055556 Tz (may ) Tj 1.4 0 Td 58.333333 Tz (be ) Tj 0.875 0 Td 51.851852 Tz (included ) Tj 2.644444 0 Td 53.472222 Tz (with ) Tj 1.458333 0 Td 49.907407 Tz (these ) Tj 1.652778 0 Td 50.555556 Tz (anticancer ) Tj 3.169444 0 Td 51.311728 Tz (agents ) Tj 2.022222 0 Td 48.611111 Tz (as ) Tj 0.777778 0 Td 46.666667 Tz (well, ) Tj 52.857143 0 0 52.857143 0 1619.634615 Tm 24.613514 0 Td 48.873874 Tz (as ) Tj 0.718919 0 Td 52.027027 Tz (long ) Tj 1.381081 0 Td 47.297297 Tz (as ) Tj 0.737838 0 Td 46.846847 Tz (neither ) Tj 2.062162 0 Td 44.144144 Tz (interferes ) Tj 2.818919 0 Td 50.45045 Tz (with ) Tj 1.381081 0 Td 46.246246 Tz (the ) Tj 0.964865 0 Td 46.569647 Tz (effectiveness ) Tj 3.745946 0 Td 56.756757 Tz (of ) Tj 0.756757 0 Td 47.297297 Tz (the ) Tj 0.945946 0 Td 50.45045 Tz (other ) Tj 51.428571 0 0 51.428571 0 1580.655738 Tm 25.297222 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 50.771605 Tz (the ) Tj 1.088889 0 Td 47.530864 Tz (user's ) Tj 1.905556 0 Td 52.5 Tz (body. ) Tj 40 0 0 40 0 1507 Tm 36.25 0 Td 63.888889 Tz (Preferred ) Tj 3.7 0 Td 78.409091 Tz (Embodiments ) Tj 5.425 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 65.277778 Tz (the ) Tj 1.45 0 Td 65.277778 Tz (Invention ) Tj 51.428571 0 0 51.428571 0 1419.533686 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.380556 0 Td 46.180556 Tz (specific ) Tj 2.469444 0 Td 61.934156 Tz (compounds ) Tj 3.577778 0 Td 52.932099 Tz (below, ) Tj 2.158333 0 Td 50.231481 Tz (as ) Tj 0.875 0 Td 51.041667 Tz (well ) Tj 1.477778 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 51.49177 Tz (following ) Tj 51.428571 0 0 51.428571 0 1377.858491 Tm 25.297222 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 55.092593 Tz (Such ) Tj 1.458333 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 57.87037 Tz (methods ) Tj 2.566667 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 52.5 Tz (using ) Tj 51.428571 0 0 51.428571 0 1335.782205 Tm 25.316667 0 Td 54.282407 Tz (Such ) Tj 1.672222 0 Td 61.574074 Tz (compounds ) Tj 3.675 0 Td 49.691358 Tz (are ) Tj 1.263889 0 Td 49.96142 Tz (non-limiting ) Tj 3.966667 0 Td 43.75 Tz (in ) Tj 0.894444 0 Td 50.231481 Tz (nature ) Tj 2.119444 0 Td 59.41358 Tz (and ) Tj 1.419444 0 Td 49.691358 Tz (are ) Tj 1.205556 0 Td 51.041667 Tz (thus ) Tj 51.428571 0 0 51.428571 0 1292.36803 Tm 25.297222 0 Td 47.314815 Tz (indicative ) Tj 2.994444 0 Td 59.953704 Tz (of ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.05 0 Td 49.691358 Tz (preferred ) Tj 2.838889 0 Td 59.511785 Tz (embodiments ) Tj 4.122222 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 43.75 Tz (this ) Tj 1.244444 0 Td 47.962963 Tz (invention. ) Tj 51.428571 0 0 51.428571 0 1252.217712 Tm 26.016667 0 Td 63.734568 Tz (The ) Tj 1.244444 0 Td 47.395833 Tz (efficacy ) Tj 2.411111 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 49.907407 Tz (these ) Tj 1.594444 0 Td 62.294239 Tz (compounds ) Tj 3.5 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 54.768519 Tz (determined ) Tj 3.402778 0 Td 59.953704 Tz (by ) Tj 0.855556 0 Td 58.981481 Tz (evalu ) Tj 51.428571 0 0 51.428571 0 1211.671498 Tm 25.297222 0 Td 47.962963 Tz (ating ) Tj 1.672222 0 Td 50.501543 Tz (fluorescence ) Tj 3.811111 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 50.411523 Tz (autotaxin ) Tj 2.936111 0 Td 43.75 Tz (at ) Tj 0.719444 0 Td 46.180556 Tz (specific ) Tj 2.45 0 Td 51.851852 Tz (wavelengths. ) Tj 3.947222 0 Td 63.734568 Tz (The ) Tj 51.428571 0 0 51.428571 0 1168.618182 Tm 25.277778 0 Td 43.75 Tz (test ) Tj 1.186111 0 Td 51.041667 Tz (protocol ) Tj 2.644444 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 48.611111 Tz (as ) Tj 0.797222 0 Td 47.800926 Tz (follows: ) Tj 51.428571 0 0 51.428571 0 1125.181929 Tm 26.036111 0 Td 55.555556 Tz (Interms ) Tj 2.469444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 75.617284 Tz (ATX ) Tj 1.516667 0 Td 46.666667 Tz (inhibition ) Tj 2.936111 0 Td 49.016204 Tz (analysis ) Tj 2.508333 0 Td 49.907407 Tz (determinations, ) Tj 4.627778 0 Td 105.864198 Tz (MDA ) Tj 51.428571 0 0 51.428571 0 1083 Tm 25.297222 0 Td 68.055556 Tz (MB-435 ) Tj 2.663889 0 Td 44.722222 Tz (cells ) Tj 1.575 0 Td 59.143519 Tz (were ) Tj 1.633333 0 Td 49.826389 Tz (cultured ) Tj 2.586111 0 Td 46.990741 Tz (at ) Tj 0.777778 0 Td 54.012346 Tz (37 ) Tj 1.225 0 Td 55.092593 Tz (C. ) Tj 0.894444 0 Td 59.41358 Tz (and ) Tj 1.302778 0 Td 77.777778 Tz (5% ) Tj 1.166667 0 Td 69.135802 Tz (CO, ) Tj 1.516667 0 Td 46.990741 Tz (in ) Tj 0.816667 0 Td 72.376543 Tz (Dul ) Tj 51.428571 0 0 51.428571 0 1041.851711 Tm 25.277778 0 Td 53.240741 Tz (becco's ) Tj 2.644444 0 Td 55.497685 Tz (Modified ) Tj 3.111111 0 Td 54.444444 Tz (Eagle ) Tj 2.022222 0 Td 67.515432 Tz (Medium ) Tj 2.877778 0 Td 76.157407 Tz (\(DMEM\) ) Tj 3.169444 0 Td 55.092593 Tz (\(MediaTech, ) Tj 51.428571 0 0 51.428571 0 1003.004926 Tm 25.316667 0 Td 56.30787 Tz (Herndon, ) Tj 2.916667 0 Td 49.421296 Tz (Va.\) ) Tj 1.4 0 Td 51.527778 Tz (containing ) Tj 3.325 0 Td 77.777778 Tz (5% ) Tj 1.186111 0 Td 42.777778 Tz (fetal ) Tj 1.516667 0 Td 55.092593 Tz (bovine ) Tj 2.216667 0 Td 58.981481 Tz (serum ) Tj 2.022222 0 Td 52.572016 Tz (\(Hyclone, ) Tj 51.428571 0 0 51.428571 0 963.212579 Tm 25.316667 0 Td 55.632716 Tz (Logan, ) Tj 2.255556 0 Td 50.231481 Tz (Utah\), ) Tj 2.080556 0 Td 58.333333 Tz (100 ) Tj 1.263889 0 Td 61.574074 Tz (U/ml ) Tj 1.691667 0 Td 43.897306 Tz (penicillin, ) Tj 3.208333 0 Td 58.333333 Tz (100 ) Tj 1.536111 0 Td 57.523148 Tz (g/ml ) Tj 1.633333 0 Td 52.662037 Tz (streptomycin ) Tj 51.428571 0 0 51.428571 0 922.981795 Tm 25.316667 0 Td 52.932099 Tz (\(Hyclone, ) Tj 3.208333 0 Td 55.092593 Tz (Logan, ) Tj 2.294444 0 Td 54.444444 Tz (Utah\) ) Tj 1.944444 0 Td 58.333333 Tz (and ) Tj 1.341667 0 Td 60.493827 Tz (292 ) Tj 1.691667 0 Td 58.333333 Tz (g/ml ) Tj 1.730556 0 Td 54.208754 Tz (L-glutamine ) Tj 3.869444 0 Td 75.617284 Tz (\(Hy ) Tj 51.428571 0 0 51.428571 0 876.887425 Tm 25.297222 0 Td 48.611111 Tz (clone, ) Tj 1.925 0 Td 55.092593 Tz (Logan, ) Tj 2.138889 0 Td 49.691358 Tz (Utah\). ) Tj 1.925 0 Td 49.907407 Tz (Cells ) Tj 1.652778 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 61.574074 Tz (grown ) Tj 1.983333 0 Td 45.37037 Tz (to ) Tj 0.680556 0 Td 71.296296 Tz (~80% ) Tj 1.866667 0 Td 52.5 Tz (confluence ) Tj 3.247222 0 Td 46.990741 Tz (at ) Tj 51.428571 0 0 51.428571 0 834.441696 Tm 25.277778 0 Td 59.62963 Tz (which ) Tj 1.886111 0 Td 55.092593 Tz (time ) Tj 1.419444 0 Td 50.771605 Tz (the ) Tj 1.011111 0 Td 43.425926 Tz (cells ) Tj 1.458333 0 Td 58.333333 Tz (were ) Tj 1.497222 0 Td 60.493827 Tz (washed ) Tj 2.294444 0 Td 52.5 Tz (twice ) Tj 1.691667 0 Td 52.662037 Tz (with ) Tj 1.380556 0 Td 42.592593 Tz (sterile ) Tj 1.886111 0 Td 55.092593 Tz (phosphate ) Tj 51.428571 0 0 51.428571 0 792.752577 Tm 25.277778 0 Td 51.041667 Tz (buffered ) Tj 2.722222 0 Td 46.990741 Tz (saline ) Tj 1.944444 0 Td 47.314815 Tz (prior ) Tj 1.691667 0 Td 43.75 Tz (to ) Tj 0.816667 0 Td 48.611111 Tz (the ) Tj 1.127778 0 Td 49.421296 Tz (addition ) Tj 2.644444 0 Td 56.712963 Tz (of ) Tj 0.855556 0 Td 57.685185 Tz (serum ) Tj 2.041667 0 Td 46.180556 Tz (free ) Tj 1.419444 0 Td 93.171296 Tz (DMEM ) Tj 51.428571 0 0 51.428571 0 753.292453 Tm 25.297222 0 Td 51.203704 Tz (containing ) Tj 3.286111 0 Td 51.58179 Tz (L-glutamine. ) Tj 3.908333 0 Td 54.79798 Tz (Conditioned ) Tj 3.811111 0 Td 64.814815 Tz (medium ) Tj 2.527778 0 Td 61.574074 Tz (was ) Tj 1.302778 0 Td 48.971193 Tz (collected ) Tj 51.428571 0 0 51.428571 0 713.252163 Tm 25.297222 0 Td 44.722222 Tz (after ) Tj 1.594444 0 Td 56.388889 Tz (24-30 ) Tj 1.925 0 Td 49.151235 Tz (hours, ) Tj 2.041667 0 Td 56.17284 Tz (supplemented ) Tj 4.297222 0 Td 52.662037 Tz (with ) Tj 1.516667 0 Td 72.376543 Tz (20% ) Tj 1.555556 0 Td 51.851852 Tz (ethylene ) Tj 2.702778 0 Td 50.771605 Tz (glycol ) Tj 51.428571 0 0 51.428571 0 670.486683 Tm 25.297222 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 61.574074 Tz (was ) Tj 1.244444 0 Td 43.930041 Tz (clarified ) Tj 2.508333 0 Td 59.953704 Tz (by ) Tj 0.855556 0 Td 48.37963 Tz (centrifugation ) Tj 4.2 0 Td 43.75 Tz (at ) Tj 0.661111 0 Td 61.574074 Tz (3000xg ) Tj 2.352778 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 59.143519 Tz (4C. ) Tj 1.575 0 Td 49.691358 Tz (for ) Tj 1.069444 0 Td 53.472222 Tz (10 ) Tj 40 0 0 40 0 634 Tm 32.575 0 Td 66.666667 Tz (min. ) Tj 2.125 0 Td 83.333333 Tz (The ) Tj 2.075 0 Td 74.166667 Tz (media ) Tj 2.75 0 Td 80.555556 Tz (was ) Tj 2 0 Td 66.319444 Tz (concentrated ) Tj 5.375 0 Td 77.777778 Tz (~10 ) Tj 1.9 0 Td 63.541667 Tz (fold ) Tj 2.05 0 Td 75 Tz (and ) Tj 1.85 0 Td 64.583333 Tz (buffer ) Tj 51.428571 0 0 51.428571 0 588.432432 Tm 25.297222 0 Td 57.613169 Tz (exchanged ) Tj 3.266667 0 Td 46.990741 Tz (into ) Tj 1.283333 0 Td 48.611111 Tz (Tris ) Tj 1.361111 0 Td 52.932099 Tz (\(50 ) Tj 1.147222 0 Td 76.697531 Tz (mM, ) Tj 1.555556 0 Td 74.537037 Tz (pH ) Tj 1.088889 0 Td 46.990741 Tz (7.4\) ) Tj 1.302778 0 Td 51.203704 Tz (containing ) Tj 3.266667 0 Td 72.376543 Tz (20% ) Tj 1.497222 0 Td 56.388889 Tz (ethyl ) Tj 51.428571 0 0 51.428571 0 543.661836 Tm 25.297222 0 Td 56.17284 Tz (ene ) Tj 1.127778 0 Td 49.691358 Tz (glycol ) Tj 1.963889 0 Td 51.851852 Tz (using ) Tj 1.672222 0 Td 56.712963 Tz (an ) Tj 0.758333 0 Td 64.274691 Tz (Amicon ) Tj 2.469444 0 Td 60.763889 Tz (8050 ) Tj 1.575 0 Td 42.939815 Tz (cell ) Tj 1.166667 0 Td 41.589506 Tz (fitted ) Tj 1.633333 0 Td 51.851852 Tz (with ) Tj 1.361111 0 Td 55.092593 Tz (a ) Tj 0.486111 0 Td 73.726852 Tz (PM30 ) Tj 1.866667 0 Td 39.429012 Tz (filter ) Tj 51.428571 0 0 51.428571 0 503.798552 Tm 25.316667 0 Td 47.727273 Tz (\(Millipore, ) Tj 3.422222 0 Td 44.074074 Tz (Billerica, ) Tj 2.877778 0 Td 50.462963 Tz (Mass.\). ) Tj 2.333333 0 Td 51.851852 Tz (Aliquots ) Tj 2.722222 0 Td 59.953704 Tz (of ) Tj 0.855556 0 Td 51.311728 Tz (concentrated ) Tj 3.927778 0 Td 72.376543 Tz (con ) Tj 40 0 0 40 0 467 Tm 32.525 0 Td 64.0625 Tz (ditioned ) Tj 3.325 0 Td 75.833333 Tz (media ) Tj 2.5 0 Td 76.041667 Tz (were ) Tj 2.075 0 Td 63.194444 Tz (stored ) Tj 2.5 0 Td 56.25 Tz (at ) Tj 0.875 0 Td 80.208333 Tz (4C. ) Tj 2.2 0 Td 56.666667 Tz (until ) Tj 2 0 Td 66.666667 Tz (needed. ) Tj 51.428571 0 0 51.428571 0 420.146341 Tm 26.016667 0 Td 78.858025 Tz (ATX ) Tj 1.75 0 Td 46.666667 Tz (inhibition ) Tj 3.15 0 Td 60.493827 Tz (was ) Tj 1.4 0 Td 54.166667 Tz (assayed ) Tj 2.605556 0 Td 52.5 Tz (using ) Tj 1.905556 0 Td 56.712963 Tz (FS-3 ) Tj 1.711111 0 Td 54.282407 Tz (\(Echelon ) Tj 2.994444 0 Td 68.055556 Tz (Bio ) Tj 51.428571 0 0 51.428571 0 376.70559 Tm 25.316667 0 Td 47.890947 Tz (sciences, ) Tj 2.780556 0 Td 41.481481 Tz (Inc., ) Tj 1.438889 0 Td 47.800926 Tz (Salt ) Tj 1.361111 0 Td 58.333333 Tz (Lake ) Tj 1.575 0 Td 46.018519 Tz (City, ) Tj 1.575 0 Td 52.5 Tz (Utah, ) Tj 1.769444 0 Td 70.486111 Tz (USA\) ) Tj 1.827778 0 Td 51.851852 Tz (as ) Tj 0.797222 0 Td 55.092593 Tz (a ) Tj 0.525 0 Td 48.251029 Tz (substrate ) Tj 2.741667 0 Td 59.41358 Tz (and ) Tj 40 0 0 40 0 343 Tm 32.525 0 Td 81.944444 Tz (~10 ) Tj 1.975 0 Td 67.5 Tz (times ) Tj 2.55 0 Td 66.666667 Tz (concentrated ) Tj 5.3 0 Td 67.424242 Tz (conditioned ) Tj 4.975 0 Td 67.916667 Tz (serum-free ) Tj 4.65 0 Td 83.333333 Tz (medium ) Tj 51.428571 0 0 51.428571 0 293 Tm 25.316667 0 Td 70 Tz (\(CCM\) ) Tj 2.411111 0 Td 57.523148 Tz (from ) Tj 1.730556 0 Td 93.981481 Tz (MDA ) Tj 2.002778 0 Td 67.515432 Tz (MB-435 ) Tj 2.780556 0 Td 44.074074 Tz (cells ) Tj 1.652778 0 Td 50.231481 Tz (as ) Tj 0.933333 0 Td 50.771605 Tz (the ) Tj 1.244444 0 Td 52.391975 Tz (source ) Tj 2.197222 0 Td 58.333333 Tz (of ) Tj 0.894444 0 Td 65.625 Tz (ATX. ) Tj 51.428571 0 0 51.428571 0 255.556604 Tm 25.297222 0 Td 56.712963 Tz (Assays ) Tj 2.177778 0 Td 59.143519 Tz (were ) Tj 1.516667 0 Td 56.532922 Tz (performed ) Tj 3.169444 0 Td 46.990741 Tz (in ) Tj 0.680556 0 Td 53.240741 Tz (96-well ) Tj 2.333333 0 Td 47.530864 Tz (plates ) Tj 1.866667 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 89.660494 Tz (CCM ) Tj 1.730556 0 Td 61.574074 Tz (compris ) Tj 51.428571 0 0 51.428571 0 210.465455 Tm 25.297222 0 Td 51.851852 Tz (ing ) Tj 1.05 0 Td 49.331276 Tz (one-third ) Tj 2.819444 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 49.691358 Tz (the ) Tj 1.030556 0 Td 42.777778 Tz (total ) Tj 1.438889 0 Td 59.953704 Tz (volume ) Tj 2.294444 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 42.777778 Tz (final ) Tj 1.477778 0 Td 55.092593 Tz (FS-3 ) Tj 1.497222 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 56.30787 Tz (charcoal ) Tj 51.428571 0 0 51.428571 0 169.836386 Tm 25.316667 0 Td 48.611111 Tz (stripped ) Tj 2.45 0 Td 44.074074 Tz (fatty ) Tj 1.438889 0 Td 51.851852 Tz (acid ) Tj 1.4 0 Td 46.180556 Tz (free ) Tj 1.283333 0 Td 75.617284 Tz (BSA ) Tj 1.477778 0 Td 50.694444 Tz (concentrations ) Tj 4.394444 0 Td 59.953704 Tz (of ) Tj 0.797222 0 Td 38.888889 Tz (1 ) Tj 0.447222 0 Td 58.333333 Tz (and ) Tj 1.166667 0 Td 61.574074 Tz (30 ) Tj 0.913889 0 Td 81.018519 Tz (uM ) Tj 1.108333 0 Td 48.611111 Tz (in ) Tj 1.428571 0 0 1.428571 0 1949 Tm 536.2 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj 114 0 obj << /Length 1 >> stream q endstream endobj 115 0 obj << /Length 20342 >> 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 57.154882 Tz (8,268,891 ) Tj 3.388636 0 Td 68.939394 Tz (B1 ) Tj 51.428571 0 0 51.428571 0 2969 Tm 14.661111 0 Td 71.296296 Tz (11 ) Tj 51.428571 0 0 51.428571 0 2914.986996 Tm 6.358333 0 Td 51.851852 Tz (assay ) Tj 1.730556 0 Td 50.231481 Tz (buffer ) Tj 1.963889 0 Td 43.75 Tz (\(1 ) Tj 0.797222 0 Td 97.222222 Tz (mM ) Tj 1.341667 0 Td 55.902778 Tz (each ) Tj 1.516667 0 Td 64.00463 Tz (CaCl ) Tj 1.944444 0 Td 59.41358 Tz (and ) Tj 1.244444 0 Td 59.953704 Tz (MgCl2, ) Tj 2.352778 0 Td 51.851852 Tz (5 ) Tj 0.544444 0 Td 98.842593 Tz (mM ) Tj 1.380556 0 Td 69.135802 Tz (KCl ) Tj 1.613889 0 Td 58.333333 Tz (140 ) Tj 51.428571 0 0 51.428571 0 2872.468193 Tm 6.358333 0 Td 100.462963 Tz (mM ) Tj 1.419444 0 Td 56.388889 Tz (NaCl, ) Tj 1.905556 0 Td 59.953704 Tz (50 ) Tj 0.913889 0 Td 100.462963 Tz (mM ) Tj 1.380556 0 Td 47.800926 Tz (Tris ) Tj 1.341667 0 Td 74.537037 Tz (pH ) Tj 1.088889 0 Td 44.074074 Tz (8.0\). ) Tj 1.555556 0 Td 53.20216 Tz (Fluorescence ) Tj 3.986111 0 Td 63.734568 Tz (was ) Tj 1.361111 0 Td 51.851852 Tz (read ) Tj 1.419444 0 Td 45.37037 Tz (at ) Tj 0.738889 0 Td 55.092593 Tz (5 ) Tj 51.428571 0 0 51.428571 0 2832.775713 Tm 6.358333 0 Td 56.17284 Tz (minute ) Tj 2.275 0 Td 45.37037 Tz (intervals ) Tj 2.683333 0 Td 59.953704 Tz (by ) Tj 0.952778 0 Td 51.851852 Tz (a ) Tj 0.583333 0 Td 57.118056 Tz (Synergy2 ) Tj 2.975 0 Td 55.092593 Tz (system ) Tj 2.275 0 Td 52.662037 Tz (\(BioTek, ) Tj 2.761111 0 Td 54.372428 Tz (Winooski, ) Tj 51.428571 0 0 51.428571 0 2789.75447 Tm 6.358333 0 Td 47.800926 Tz (Vt.\) ) Tj 1.283333 0 Td 52.662037 Tz (with ) Tj 1.4 0 Td 47.314815 Tz (excitation ) Tj 2.955556 0 Td 59.41358 Tz (and ) Tj 1.205556 0 Td 53.06713 Tz (emission ) Tj 2.722222 0 Td 54.208754 Tz (wavelengths ) Tj 3.675 0 Td 58.333333 Tz (of ) Tj 0.777778 0 Td 58.333333 Tz (485 ) Tj 1.186111 0 Td 58.333333 Tz (and ) Tj 1.186111 0 Td 59.41358 Tz (538 ) Tj 51.428571 0 0 51.428571 0 2749.620347 Tm 6.358333 0 Td 61.574074 Tz (nm, ) Tj 1.283333 0 Td 46.118234 Tz (respectively. ) Tj 3.811111 0 Td 50 Tz (Results ) Tj 2.275 0 Td 48.611111 Tz (are ) Tj 1.069444 0 Td 61.574074 Tz (shown ) Tj 2.002778 0 Td 46.990741 Tz (at ) Tj 0.777778 0 Td 35.648148 Tz (1 ) Tj 0.447222 0 Td 49.907407 Tz (hour, ) Tj 1.652778 0 Td 46.990741 Tz (at ) Tj 0.7 0 Td 58.981481 Tz (which ) Tj 1.925 0 Td 51.203704 Tz (point ) Tj 51.428571 0 0 51.428571 0 2706.227621 Tm 6.358333 0 Td 39.969136 Tz (all ) Tj 0.991667 0 Td 50.501543 Tz (fluorescence ) Tj 3.888889 0 Td 55.555556 Tz (changes ) Tj 2.586111 0 Td 50.231481 Tz (as ) Tj 0.855556 0 Td 58.333333 Tz (a ) Tj 0.583333 0 Td 50.231481 Tz (function ) Tj 2.702778 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 54.282407 Tz (time ) Tj 1.575 0 Td 58.333333 Tz (were ) Tj 1.652778 0 Td 42.12963 Tz (linear. ) Tj 51.428571 0 0 51.428571 0 2665.236908 Tm 6.377778 0 Td 53.20216 Tz (Fluorescence ) Tj 4.161111 0 Td 50.231481 Tz (readings ) Tj 2.702778 0 Td 59.143519 Tz (were ) Tj 1.75 0 Td 54.12037 Tz (normalized ) Tj 3.538889 0 Td 45.37037 Tz (to ) Tj 0.894444 0 Td 49.537037 Tz (vehicle ) Tj 2.333333 0 Td 49.074074 Tz (control ) Tj 40 0 0 40 0 2630 Tm 8.175 0 Td 58.333333 Tz (after ) Tj 1.9 0 Td 62.5 Tz (subtraction ) Tj 4.3 0 Td 70.833333 Tz (of ) Tj 0.925 0 Td 65.277778 Tz (fluorescence ) Tj 4.875 0 Td 58.333333 Tz (in ) Tj 0.85 0 Td 63.888889 Tz (the ) Tj 1.3 0 Td 70.833333 Tz (absence ) Tj 3.125 0 Td 72.916667 Tz (of ) Tj 0.975 0 Td 93.75 Tz (CCM. ) Tj 2.5 0 Td 71.875 Tz (Data ) Tj 40 0 0 40 0 2589 Tm 8.175 0 Td 63.888889 Tz (are ) Tj 1.4 0 Td 79.166667 Tz (shown ) Tj 2.625 0 Td 64.583333 Tz (as ) Tj 1.025 0 Td 63.888889 Tz (the ) Tj 1.425 0 Td 76.388889 Tz (meantS.D. ) Tj 4.375 0 Td 75 Tz (of ) Tj 1.025 0 Td 56.25 Tz (at ) Tj 0.925 0 Td 56.666667 Tz (least ) Tj 1.925 0 Td 62.5 Tz (three ) Tj 2.125 0 Td 59.722222 Tz (wells. ) Tj 51.428571 0 0 51.428571 0 2540.709317 Tm 7.116667 0 Td 59.143519 Tz (Each ) Tj 1.575 0 Td 56.712963 Tz (of ) Tj 0.758333 0 Td 50.771605 Tz (the ) Tj 1.05 0 Td 51.851852 Tz (nine ) Tj 1.380556 0 Td 61.934156 Tz (compounds ) Tj 3.519444 0 Td 54.444444 Tz (determined ) Tj 3.402778 0 Td 48.611111 Tz (for ) Tj 0.991667 0 Td 46.450617 Tz (effective ) Tj 2.625 0 Td 77.777778 Tz (ATX ) Tj 51.428571 0 0 51.428571 0 2499.563591 Tm 6.358333 0 Td 46.990741 Tz (inhibition ) Tj 3.130556 0 Td 53.703704 Tz (through ) Tj 2.605556 0 Td 48.611111 Tz (the ) Tj 1.186111 0 Td 57.118056 Tz (modeling ) Tj 3.072222 0 Td 59.953704 Tz (method ) Tj 2.45 0 Td 50.231481 Tz (delineated ) Tj 3.305556 0 Td 57.685185 Tz (above ) Tj 51.428571 0 0 51.428571 0 2459.68984 Tm 6.338889 0 Td 59.953704 Tz (were ) Tj 1.925 0 Td 54.73251 Tz (purchased ) Tj 3.422222 0 Td 57.523148 Tz (from ) Tj 1.886111 0 Td 62.546296 Tz (ChemBridge ) Tj 4.238889 0 Td 55.740741 Tz (under ) Tj 2.158333 0 Td 47.530864 Tz (the ) Tj 1.361111 0 Td 59.259259 Tz (numbers ) Tj 51.428571 0 0 51.428571 0 2416.745308 Tm 6.358333 0 Td 51.851852 Tz (assigned ) Tj 2.683333 0 Td 57.685185 Tz (above ) Tj 1.905556 0 Td 58.333333 Tz (and ) Tj 1.225 0 Td 47.222222 Tz (herein. ) Tj 51.428571 0 0 51.428571 0 2375.685315 Tm 7.097222 0 Td 75.833333 Tz (TABLE ) Tj 2.663889 0 Td 38.888889 Tz (1 ) Tj 0.602778 0 Td 52.256944 Tz (provides ) Tj 2.858333 0 Td 49.691358 Tz (the ) Tj 1.186111 0 Td 77.777778 Tz (ATX ) Tj 1.730556 0 Td 44.965278 Tz (activity ) Tj 2.527778 0 Td 49.907407 Tz (reductions ) Tj 3.344444 0 Td 42.12963 Tz (\(at ) Tj 1.147222 0 Td 56.712963 Tz (10 ) Tj 51.428571 0 0 51.428571 0 2332.344103 Tm 6.358333 0 Td 58.693416 Tz (micromole ) Tj 3.344444 0 Td 49.691358 Tz (concentrations\) ) Tj 4.666667 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 49.907407 Tz (these ) Tj 1.652778 0 Td 48.148148 Tz (assays. ) Tj 38.571429 0 0 38.571429 0 2252 Tm 18.251852 0 Td 101.111111 Tz (TABLE ) Tj 3.37037 0 Td 23.765432 Tz (1. ) Tj 31.428571 0 0 31.428571 0 2185 Tm 21.827273 0 Td 100.757576 Tz (ATX ) Tj 2.068182 0 Td 60.984848 Tz (Inhibition ) Tj 40 0 0 40 0 2117.406557 Tm 13.275 0 Td 67.708333 Tz (Compound ) Tj 8.2 0 Td 100 Tz (% ) Tj 0.75 0 Td 79.166667 Tz (ATX ) Tj 1.6 0 Td 48.958333 Tz (Activity ) Tj 35.142857 0 0 35.142857 0 2082.330579 Tm 15.109756 0 Td 73.509485 Tz (ID ) Tj 1.052846 0 Td 75.880759 Tz (# ) Tj 9.447154 0 Td 52.168022 Tz (at ) Tj 0.853659 0 Td 64.02439 Tz (10 ) Tj 1.422764 0 Td 118.563686 Tz (M ) Tj 30 0 0 30 0 2024 Tm 17.7 0 Td 80.15873 Tz (7839888 ) Tj 12.8 0 Td 75 Tz (41 ) Tj 1.3 0 Td 27.777778 Tz (- ) Tj 0.666667 0 Td 83.333333 Tz (9 ) Tj 30 0 0 30 0 1991 Tm 17.7 0 Td 80.15873 Tz (SS64949 ) Tj 12.8 0 Td 77.777778 Tz (45 ) Tj 1.3 0 Td 27.777778 Tz (- ) Tj 0.766667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 1958 Tm 17.7 0 Td 79.365079 Tz (5711925 ) Tj 12.8 0 Td 135.185185 Tz (485 ) Tj 30 0 0 30 0 1924 Tm 17.7 0 Td 80.15873 Tz (S186522 ) Tj 12.8 0 Td 80.555556 Tz (49 ) Tj 1.3 0 Td 27.777778 Tz (- ) Tj 0.766667 0 Td 75 Tz (10 ) Tj 30 0 0 30 0 1891 Tm 17.7 0 Td 79.365079 Tz (5761473 ) Tj 12.8 0 Td 80.555556 Tz (46 ) Tj 2.066667 0 Td 66.666667 Tz (6 ) Tj 30 0 0 30 0 1858 Tm 17.7 0 Td 80.952381 Tz (SS38444 ) Tj 12.833333 0 Td 72.222222 Tz (31 ) Tj 1.266667 0 Td 27.777778 Tz (- ) Tj 0.666667 0 Td 88.888889 Tz (4 ) Tj 30 0 0 30 0 1825 Tm 17.7 0 Td 69.444444 Tz (79.21385 ) Tj 12.833333 0 Td 72.222222 Tz (21 ) Tj 2 0 Td 72.222222 Tz (6 ) Tj 30 0 0 30 0 1791 Tm 17.7 0 Td 80.952381 Tz (5210574 ) Tj 12.833333 0 Td 133.333333 Tz (315 ) Tj 30 0 0 30 0 1758 Tm 17.7 0 Td 80.15873 Tz (7905958 ) Tj 13.3 0 Td 77.777778 Tz (O ) Tj 1.5 0 Td 83.333333 Tz (4 ) Tj 51.428571 0 0 51.428571 0 1650.827357 Tm 7.097222 0 Td 53.796296 Tz (Thus, ) Tj 1.886111 0 Td 34.027778 Tz (it ) Tj 0.7 0 Td 37.268519 Tz (is ) Tj 0.7 0 Td 51.388889 Tz (evident ) Tj 2.430556 0 Td 44.560185 Tz (that ) Tj 1.322222 0 Td 49.691358 Tz (the ) Tj 1.166667 0 Td 49.331276 Tz (inventive ) Tj 2.897222 0 Td 61.934156 Tz (compounds ) Tj 3.597222 0 Td 48.611111 Tz (exhibit ) Tj 51.428571 0 0 51.428571 0 1609.850467 Tm 6.358333 0 Td 48.611111 Tz (excellent ) Tj 2.761111 0 Td 47.170782 Tz (potential ) Tj 2.702778 0 Td 49.691358 Tz (for ) Tj 0.991667 0 Td 50.411523 Tz (autotaxin ) Tj 2.877778 0 Td 45.868946 Tz (inactivation, ) Tj 3.713889 0 Td 46.990741 Tz (particularly ) Tj 3.538889 0 Td 49.691358 Tz (the ) Tj 51.428571 0 0 51.428571 0 1569.014068 Tm 6.358333 0 Td 60.185185 Tz (7905958 ) Tj 2.644444 0 Td 64.409722 Tz (compound ) Tj 3.227778 0 Td 51.851852 Tz (with ) Tj 1.361111 0 Td 46.548822 Tz (essentially ) Tj 3.247222 0 Td 55.092593 Tz (no ) Tj 0.777778 0 Td 77.777778 Tz (ATX ) Tj 1.497222 0 Td 44.965278 Tz (activity ) Tj 2.313889 0 Td 50.636574 Tz (detected ) Tj 51.428571 0 0 51.428571 0 1528.525773 Tm 6.358333 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 36.458333 Tz (all. ) Tj 1.186111 0 Td 55.092593 Tz (Coupled, ) Tj 2.916667 0 Td 48.611111 Tz (again, ) Tj 2.061111 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 48.611111 Tz (the ) Tj 1.166667 0 Td 46.990741 Tz (oral ) Tj 1.419444 0 Td 46.018519 Tz (bioavailability ) Tj 4.472222 0 Td 44.444444 Tz (results ) Tj 51.428571 0 0 51.428571 0 1486.603136 Tm 6.358333 0 Td 54.444444 Tz (noted ) Tj 1.769444 0 Td 52.932099 Tz (above, ) Tj 2.061111 0 Td 50.555556 Tz (these ) Tj 1.711111 0 Td 61.574074 Tz (compounds ) Tj 3.5 0 Td 69.135802 Tz (who ) Tj 1.4 0 Td 49.259259 Tz (great ) Tj 1.652778 0 Td 56.018519 Tz (promise ) Tj 2.508333 0 Td 45.37037 Tz (in ) Tj 0.738889 0 Td 58.873457 Tz (provid ) Tj 51.428571 0 0 51.428571 0 1442.854271 Tm 6.358333 0 Td 50.771605 Tz (ing ) Tj 1.127778 0 Td 46.450617 Tz (orally ) Tj 1.886111 0 Td 48.935185 Tz (ingestable ) Tj 3.111111 0 Td 58.981481 Tz (tumor ) Tj 1.905556 0 Td 50.555556 Tz (treatments ) Tj 3.227778 0 Td 48.611111 Tz (for ) Tj 1.030556 0 Td 46.759259 Tz (certain ) Tj 2.177778 0 Td 48.206019 Tz (cancers. ) Tj 51.428571 0 0 51.428571 0 1399.820513 Tm 7.097222 0 Td 56.388889 Tz (There ) Tj 1.925 0 Td 44.560185 Tz (are, ) Tj 1.322222 0 Td 56.712963 Tz (of ) Tj 0.836111 0 Td 49.074074 Tz (course, ) Tj 2.352778 0 Td 64.814815 Tz (many ) Tj 1.808333 0 Td 46.254209 Tz (alternative ) Tj 3.247222 0 Td 59.806397 Tz (embodiments ) Tj 4.161111 0 Td 61.574074 Tz (and ) Tj 51.428571 0 0 51.428571 0 1358.050602 Tm 6.358333 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 50.462963 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 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 1317.700787 Tm 6.338889 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 41.589506 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 47.638889 Tz (invention. ) Tj 40 0 0 40 0 1278 Tm 9.125 0 Td 102.083333 Tz (We ) Tj 1.45 0 Td 63.194444 Tz (claim: ) Tj 51.428571 0 0 51.428571 0 1231.905512 Tm 7.136111 0 Td 38.888889 Tz (1. ) Tj 0.7 0 Td 84.259259 Tz (A ) Tj 0.777778 0 Td 59.41358 Tz (method ) Tj 2.372222 0 Td 48.611111 Tz (for ) Tj 1.088889 0 Td 46.990741 Tz (inhibiting ) Tj 3.033333 0 Td 50.411523 Tz (autotaxin ) Tj 2.916667 0 Td 45.37037 Tz (activity ) Tj 2.430556 0 Td 53.240741 Tz (through ) Tj 2.508333 0 Td 48.611111 Tz (the ) Tj 51.428571 0 0 51.428571 0 1188.612091 Tm 6.358333 0 Td 48.611111 Tz (reaction ) Tj 2.625 0 Td 56.712963 Tz (of ) Tj 0.855556 0 Td 50.05144 Tz (autotaxin ) Tj 2.975 0 Td 52.662037 Tz (with ) Tj 1.555556 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 44.722222 Tz (least ) Tj 1.594444 0 Td 58.333333 Tz (one ) Tj 1.302778 0 Td 50.231481 Tz (thiourea ) Tj 2.663889 0 Td 64.814815 Tz (compound ) Tj 51.428571 0 0 51.428571 0 1147.447059 Tm 6.338889 0 Td 56.018519 Tz (wherein ) Tj 2.508333 0 Td 48.611111 Tz (said ) Tj 1.302778 0 Td 49.826389 Tz (thiourea ) Tj 2.547222 0 Td 64.00463 Tz (compound ) Tj 3.188889 0 Td 47.800926 Tz (exhibits ) Tj 2.430556 0 Td 58.333333 Tz (a ) Tj 0.505556 0 Td 54.012346 Tz (molecular ) Tj 3.033333 0 Td 55.092593 Tz (weight ) Tj 51.428571 0 0 51.428571 0 1105.59 Tm 6.358333 0 Td 58.333333 Tz (of ) Tj 0.816667 0 Td 43.75 Tz (at ) Tj 0.777778 0 Td 58.333333 Tz (most ) Tj 1.613889 0 Td 51.851852 Tz (527, ) Tj 1.477778 0 Td 55.092593 Tz (wherein ) Tj 2.547222 0 Td 49.421296 Tz (said ) Tj 1.4 0 Td 49.016204 Tz (thiourea ) Tj 2.566667 0 Td 64.409722 Tz (compound ) Tj 3.305556 0 Td 50.231481 Tz (includes ) Tj 2.644444 0 Td 55.092593 Tz (a ) Tj 51.428571 0 0 51.428571 0 1066.018648 Tm 6.338889 0 Td 50.636574 Tz (terminal ) Tj 2.566667 0 Td 51.557239 Tz (carboxylate ) Tj 3.538889 0 Td 51.851852 Tz (group; ) Tj 2.022222 0 Td 55.555556 Tz (wherein ) Tj 2.488889 0 Td 48.611111 Tz (said ) Tj 1.283333 0 Td 49.421296 Tz (thiourea ) Tj 2.508333 0 Td 64.814815 Tz (compound ) Tj 51.428571 0 0 51.428571 0 1023.88589 Tm 6.358333 0 Td 56.388889 Tz (meets ) Tj 1.905556 0 Td 39.969136 Tz (all ) Tj 0.913889 0 Td 55.092593 Tz (extended ) Tj 2.838889 0 Td 42.718855 Tz (flexibility ) Tj 3.072222 0 Td 49.537037 Tz (metrics ) Tj 2.275 0 Td 61.574074 Tz (of ) Tj 0.875 0 Td 48.287037 Tz (Lipinski's ) Tj 3.130556 0 Td 46.666667 Tz (rules ) Tj 1.633333 0 Td 47.530864 Tz (for ) Tj 51.428571 0 0 51.428571 0 981.921084 Tm 6.338889 0 Td 48.611111 Tz (biological ) Tj 3.091667 0 Td 45.121083 Tz (distribution; ) Tj 3.694444 0 Td 59.41358 Tz (and ) Tj 1.225 0 Td 55.555556 Tz (wherein ) Tj 2.527778 0 Td 48.611111 Tz (said ) Tj 1.322222 0 Td 49.826389 Tz (thiourea ) Tj 2.547222 0 Td 64.814815 Tz (compound ) Tj 51.428571 0 0 51.428571 0 938.510204 Tm 6.358333 0 Td 47.395833 Tz (exhibits ) Tj 2.586111 0 Td 56.712963 Tz (an ) Tj 0.972222 0 Td 49.691358 Tz (autotaxin ) Tj 3.013889 0 Td 46.342593 Tz (inhibition ) Tj 3.072222 0 Td 47.962963 Tz (capability ) Tj 3.15 0 Td 59.953704 Tz (of ) Tj 0.894444 0 Td 45.37037 Tz (at ) Tj 0.816667 0 Td 45.37037 Tz (least ) Tj 1.633333 0 Td 73.45679 Tz (59% ) Tj 51.428571 0 0 51.428571 0 897.223529 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.586111 0 Td 58.333333 Tz (a ) Tj 0.680556 0 Td 50.411523 Tz (reduction ) Tj 3.072222 0 Td 45.37037 Tz (in ) Tj 0.875 0 Td 48.251029 Tz (available ) Tj 2.916667 0 Td 48.611111 Tz (reaction ) Tj 2.663889 0 Td 42.777778 Tz (sites ) Tj 1.594444 0 Td 52.314815 Tz (thereon ) Tj 2.527778 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 858.587544 Tm 6.358333 0 Td 51.388889 Tz (prevent ) Tj 2.333333 0 Td 50.05144 Tz (autotaxin ) Tj 2.936111 0 Td 51.851852 Tz (conversion ) Tj 3.325 0 Td 56.712963 Tz (of ) Tj 0.797222 0 Td 53.119968 Tz (lysophosphatidylcholine ) Tj 7.505556 0 Td 46.990741 Tz (to ) Tj 51.428571 0 0 51.428571 0 815.555556 Tm 6.358333 0 Td 51.244213 Tz (lysophosphatidic ) Tj 5.347222 0 Td 46.666667 Tz (acid, ) Tj 1.827778 0 Td 55.092593 Tz (wherein ) Tj 2.741667 0 Td 49.421296 Tz (said ) Tj 1.575 0 Td 50.411523 Tz (autotaxin ) Tj 3.15 0 Td 47.638889 Tz (inhibition ) Tj 51.428571 0 0 51.428571 0 773.442604 Tm 6.358333 0 Td 47.638889 Tz (capability ) Tj 3.013889 0 Td 49.826389 Tz (involves ) Tj 2.566667 0 Td 44.965278 Tz (ligation ) Tj 2.352778 0 Td 53.472222 Tz (of ) Tj 0.7 0 Td 50.411523 Tz (autotaxin ) Tj 2.858333 0 Td 48.070988 Tz (active ) Tj 1.866667 0 Td 42.12963 Tz (site ) Tj 1.186111 0 Td 54.012346 Tz (metalions ) Tj 51.428571 0 0 51.428571 0 732.129353 Tm 6.338889 0 Td 54.166667 Tz (through ) Tj 2.488889 0 Td 49.691358 Tz (the ) Tj 1.088889 0 Td 50.231481 Tz (thiourea ) Tj 2.605556 0 Td 48.935185 Tz (functional ) Tj 3.15 0 Td 52.391975 Tz (group, ) Tj 2.080556 0 Td 51.851852 Tz (as ) Tj 0.836111 0 Td 51.851852 Tz (well ) Tj 1.458333 0 Td 51.851852 Tz (as ) Tj 0.816667 0 Td 49.691358 Tz (the ) Tj 1.108333 0 Td 61.574074 Tz (simul ) Tj 51.428571 0 0 51.428571 0 689.622248 Tm 6.338889 0 Td 53.703704 Tz (taneous ) Tj 2.352778 0 Td 45.121083 Tz (electrostatic ) Tj 3.655556 0 Td 46.990741 Tz (interactions ) Tj 3.538889 0 Td 53.472222 Tz (of ) Tj 0.719444 0 Td 47.800926 Tz (said ) Tj 1.263889 0 Td 50.636574 Tz (terminal ) Tj 2.566667 0 Td 51.557239 Tz (carboxylate ) Tj 51.428571 0 0 51.428571 0 648.953846 Tm 6.358333 0 Td 56.388889 Tz (group ) Tj 1.905556 0 Td 52.662037 Tz (with ) Tj 1.438889 0 Td 50.05144 Tz (autotaxin ) Tj 2.897222 0 Td 48.611111 Tz (constituent ) Tj 3.363889 0 Td 46.450617 Tz (proteins. ) 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 51.428571 0 0 51.428571 0 2969 Tm 33.6 0 Td 72.916667 Tz (12 ) Tj 40 0 0 40 0 2921 Tm 33.45 0 Td 56.25 Tz (2. ) Tj 0.85 0 Td 81.944444 Tz (The ) Tj 1.675 0 Td 77.083333 Tz (method ) Tj 2.975 0 Td 68.75 Tz (of ) Tj 0.925 0 Td 68.333333 Tz (claim ) Tj 2.275 0 Td 62.5 Tz (1 ) Tj 0.65 0 Td 70.833333 Tz (wherein ) Tj 3.175 0 Td 62.5 Tz (said ) Tj 1.675 0 Td 58.333333 Tz (at ) Tj 0.85 0 Td 57.5 Tz (least ) Tj 1.925 0 Td 73.611111 Tz (one ) Tj 1.5 0 Td 64.0625 Tz (thiourea ) Tj 51.428571 0 0 51.428571 0 2878.537143 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.266667 0 Td 38.888889 Tz (is ) Tj 0.661111 0 Td 48.611111 Tz (selected ) Tj 2.508333 0 Td 58.333333 Tz (from ) Tj 1.594444 0 Td 50.771605 Tz (the ) Tj 1.069444 0 Td 56.388889 Tz (group ) Tj 1.886111 0 Td 49.259259 Tz (consisting ) Tj 3.130556 0 Td 43.209877 Tz (of: ) Tj 40 0 0 40 0 2758.379913 Tm 49.05 0 Td 67.1875 Tz (Compound ) Tj 3.45 0 Td 59.52381 Tz (7905958 ) Tj 31.428571 0 0 31.428571 0 2701 Tm 68.822727 0 Td 111.363636 Tz (C ) Tj 31.428571 0 0 31.428571 0 2609 Tm 62.490909 0 Td 106.060606 Tz (H ) Tj 168.571429 0 0 168.571429 0 2490 Tm 11.194068 0 Td 64.265537 Tz (- ) Tj 31.428571 0 0 31.428571 0 2471 Tm 62.522727 0 Td 74.242424 Tz (S ) Tj 6.3 0 Td 111.363636 Tz (C ) Tj 40 0 0 40 0 2208.379913 Tm 49.05 0 Td 67.1875 Tz (Compound ) Tj 3.45 0 Td 59.52381 Tz (7839888 ) Tj 31.428571 0 0 31.428571 0 2131 Tm 61.822727 0 Td 111.363636 Tz (O ) Tj 31.428571 0 0 31.428571 0 1920 Tm 65.513636 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 1397.394737 Tm 49.05 0 Td 67.1875 Tz (Compound ) Tj 3.45 0 Td 58.928571 Tz (7921385 ) Tj 31.428571 0 0 31.428571 0 974 Tm 67.072727 0 Td 111.363636 Tz (O ) Tj 40 0 0 40 0 912 Tm 33.45 0 Td 56.25 Tz (3. ) Tj 0.85 0 Td 81.944444 Tz (The ) Tj 1.675 0 Td 77.083333 Tz (method ) Tj 2.975 0 Td 68.75 Tz (of ) Tj 0.925 0 Td 68.333333 Tz (claim ) Tj 2.275 0 Td 62.5 Tz (1 ) Tj 0.65 0 Td 70.833333 Tz (wherein ) Tj 3.175 0 Td 62.5 Tz (said ) Tj 1.675 0 Td 58.333333 Tz (at ) Tj 0.85 0 Td 57.5 Tz (least ) Tj 1.925 0 Td 73.611111 Tz (one ) Tj 1.5 0 Td 64.0625 Tz (thiourea ) Tj 51.428571 0 0 51.428571 0 868.032419 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.325 0 Td 47.800926 Tz (exhibits ) Tj 2.566667 0 Td 56.712963 Tz (an ) Tj 0.972222 0 Td 49.691358 Tz (autotaxin ) Tj 2.975 0 Td 46.666667 Tz (inhibition ) Tj 3.111111 0 Td 47.314815 Tz (capability ) Tj 3.130556 0 Td 56.712963 Tz (of ) Tj 0.855556 0 Td 45.37037 Tz (at ) Tj 40 0 0 40 0 833 Tm 32.525 0 Td 57.5 Tz (least ) Tj 1.95 0 Td 70 Tz (about ) Tj 2.3 0 Td 80.208333 Tz (79%. ) Tj 40 0 0 40 0 794 Tm 33.45 0 Td 56.25 Tz (4. ) Tj 0.85 0 Td 81.944444 Tz (The ) Tj 1.675 0 Td 77.083333 Tz (method ) Tj 2.975 0 Td 68.75 Tz (of ) Tj 0.925 0 Td 68.333333 Tz (claim ) Tj 2.275 0 Td 62.5 Tz (1 ) Tj 0.65 0 Td 70.833333 Tz (wherein ) Tj 3.175 0 Td 62.5 Tz (said ) Tj 1.675 0 Td 58.333333 Tz (at ) Tj 0.85 0 Td 57.5 Tz (least ) Tj 1.925 0 Td 73.611111 Tz (one ) Tj 1.5 0 Td 64.0625 Tz (thiourea ) Tj 51.428571 0 0 51.428571 0 748.846512 Tm 25.297222 0 Td 64.00463 Tz (compound ) Tj 3.188889 0 Td 47.800926 Tz (exhibits ) Tj 2.391667 0 Td 58.333333 Tz (an ) Tj 0.797222 0 Td 50.05144 Tz (autotaxin ) Tj 2.838889 0 Td 46.666667 Tz (inhibition ) Tj 2.916667 0 Td 47.962963 Tz (capability ) Tj 2.994444 0 Td 55.092593 Tz (of ) Tj 0.738889 0 Td 53.796296 Tz (about ) Tj 38.571429 0 0 38.571429 0 715 Tm 33.807407 0 Td 79.506173 Tz (100%. ) Tj 1.428571 0 0 1.428571 0 1916 Tm 941.5 0 Td 116.666667 Tz ( ) Tj 1.428571 0 0 1.428571 0 1366 Tm 912.8 0 Td 116.666667 Tz ( ) Tj ET Q endstream endobj xref 3 1 0000515122 00000 n 17 1 0000515429 00000 n 31 1 0000515740 00000 n 45 1 0000516051 00000 n 59 1 0000516362 00000 n 73 1 0000516673 00000 n 87 1 0000516984 00000 n 102 14 0000517295 00000 n 0000517348 00000 n 0000530965 00000 n 0000531018 00000 n 0000569913 00000 n 0000569966 00000 n 0000591018 00000 n 0000591071 00000 n 0000637165 00000 n 0000637218 00000 n 0000652380 00000 n 0000652433 00000 n 0000690254 00000 n 0000690307 00000 n trailer << /Size 116 /Prev 512857 /Info 101 0 R /Root 1 0 R /ID [ (d\000uO-\nyhO=%_̙) (d\000uO-\nyhO=%_̙) ] >> startxref 710705 %%EOF