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b5fHDItXJUB5kmpSUpFleK3PPnj3UqlUrB06Q/6pXyVrXmZGXc36f8NNw4EsbPdXORkWL2Em3UlkbwU/DnfXtx/6KGhIX1jFjOEFvg4k36FPgWQeGDx8uHki87u7bt0+shqEJsH+/dcOonD17VpAPVrcgrxo1arjc9XeFBAjMTPkvVuh333236Dd0bv/880/d7mFzrHHjxg7ChHz+r7/+0i3v7oQV5b8w3Bk/5DqqXNZOsMWL2gn40CS73wUjZLzw1XDxyFR38ITFeSbeEJlGqFiBvOrWrUufffYZSRUmkBo2eOADwCoJlnd4HVfLLmEc4m+CGEa+AQCPQMp/0RYs6vQS1MPw4yfnAqpwWPUakaAJAdm31JwIpvwXb1k333yz44el1U022jDG2dHNq11s1PkOG+3+xDlfbpjhc9Jge5kFr2mXQQghyss2Aj7L18HEa/kpsndQmppiZYUErQCsAKWKEkgImgEgvGAaWWAjEGSI/uAPPwonTpwwHOVgyn8lKZYtW1aMEXOADcPMzEzDxynlv/Kt4aqrrhIWcmbo/0Ke3r17d8dcQu3vu3EP6rqGVJKst9/hj/dy/GbD8bNqhUy8FpkZKTscOXIkQbc1KyvL0TOoGWFXHET2xhtvOPLxBbJOkC1WW5LsqlatKvRKsSIzK8HKDgEcZR8aNGgQcE2EYMh/QfjXXXedY5z4YdFziGMk9pD/StEHML711lsDJv+9ePGi+CGRm7vR0dHiGPdkfm4mCQ0HxUabtySrLh8fG03pf35gJFyWr4uJ1wJThNUSDCewqpW74VDKB3lBtCDzWrRoQXqv63i9h4cvlJHkh9dTvAq7kk/6O3y9XX8znflIWbI7/V8EmsTruytxAHxGoEx8fLwTNGr1MGx8QfXP7KRF/Gr9X/iMgHMlaMbgvtBKH330kSjz+++/O05Dro176NprrxX3EEQouH/i4uIcZfAlLyuZEhfVNyT8D7QYENUi0hITb5Bn/JtvvhE3OUgDDxVIBCvYRx55hG677TahDQBd3mnTpnnsmQyrIzwwkrBBxHfddZd4qIx6RZW7+N6ohwUaarX8V20V9tRTTzkIRWqHqPvUqVMnUQa6xEi+qIep6zT6WIo69OS/sPqTP74ff/yxZvP9+vUTZSQOwA73iLyuWbNm9Msvv2hei0xYs6WsecjnKMNwqC5irUWAzq4WiJYj3iMXkuiLA1vpkXXTqfaC96lMzEiyTR/m+MPxdQvep85rp9HE/VvoUGroWnctW7bMQY5ffPGF1vz4lQfZKkxZoXsqHyisoEHsMGTwNUE9TLmyduUUxtc2/LkOP2BqazHIKyXxAosbbrjBSZwj25PEix8vf9XDZJ2B+tST/0oNGPzwQkxw6tSpQl2QxAvdcOCilCFj3Hr+JtQVXToWQ/FzK1NcbFmHjq9alOB0PDOK4mdHU/Ky5pRz3roaOepxGn1sCeJNz84SJCqJtvSs1x1EqyRd9XeUi44ZSbUWjKHx+zZRWvZ/clGjgTK6PpAXHgqQAEQNgUwQT+D1E5tvkoChcYDNOW/kk2qnMP6ohwVyvKgbq8IxY8aQ3ADDrrwkXsQ7Aw7vv/9+oW5I4p06daoDK5S3su+M3bt3O+S/WOVL4oUeMcYJFUR1ksSLyB/ASOpH+2I1l5+bRRePfEtJPzUVRhbxcyoQVMPiZpUS4oi42eVJ/MWWoXPru9Ll+C3q7kTccVCJNzc/jybs30zlY98UBKomVm+OQcDlYt+gj/duoByLm9dCNQwbYHgoQAZmJYgHsBqE/E8SsFRH27p1q2435CaWfLV15xRGt6IgnMCPRf/+/WnJkiUO4oX5MWTqGIdaPiqJF6IG/DAh2GYoJKxQZ8+eLcQDUtSAviPSBeYa0ZqVSRIvRA1QmYOWjBEpP/sCXY7bQJeOzqCMfZ9QxoHP6dKJeYRAmZESyNITHINGvMfSkqnhjx9T2Zg3PFrdekrC0bEjqf4PH9HhC9YUQcDxzfXXXy8eBrgINHMTSnlDgFiwIpI713g4IVPGa6ayTyBqtVOYQKiHKfsWqO9yxYtNsZiYGDEH8KegTEriVeaH0ncl8cLABqtZaL0orR2VxBtKYwuXvgaFeDfGHaNysW9S0RmvGkq6kpyLzBguCH3dWWN+xY2abLzy41UQJHf77bf7JWc1qk9QOYMKGzyByVVwrVq1hFtGWGDJvEaNGgmtC6PaDUY9SuLFClGaMeN1W6ZwI16MCyt3zCOc7MvExCuRCM6n6cS7Ke6432IFSbDuPrERZxXyhVqP9FaFDS5XzmGCcStARxOr3YYNG4qHVK6EpVMY5So4GP0zok0l8aI+mPViA6p69eoEtTikcCRe6HpjjBirdLDPxGvEHeV7HaYS74m0FLHSFYT5xRCyvd6DbB8M1F/1Tn3FXmZUX3uZcU+TbXg3sr3ZS/+aD560l5nwnCgDUQY0JYKZsLqCnBGrDjhRMUqeFogxoa/jx48XfYU+pzTsCERbZtepJl60L1eDCCaKFI7Ei3HFxsaKOYXKGOaYiVdMd9D+mUa8+ZRPTReP/0+88FIXcSPY7rxRn0QnPm8vU72SvUxXu9MSW5SNbCN7al/X9lb7NUM6i/MQOzRc9DHl6YRjMQN5KXPD5hT0Ja2eZPyzzp07W72rXvVPi3ixi4+NNqwG4XwoXIkXZAtnP/jxh5EEE69Xt47hhU0j3nknfqeysYqNNH+IF34AalxBNqyIFTq+4ruKeJFXNmYkzTy6y3DwPKlw0qRJ4mbHBocrx9me1GVWGegU4wEdPHiwWU2a0o4W8aLhOXPmiPHC/DdciRfjlBttMHl+/PHHxZilAYUpE8CNOBAwjXivX/ihM0n6Q7xXVRY3ja37Pc51goQ1iBfkW2v+GMegzfoCdR5YpMH0csaMGWY163c78AcB4kWcsHBKesSL1aDcSIQsFGOXlmuhOH75hqWlCgeDGowPqnT4ZOINzgybQrz7zscV3lDzh3ifaEu2CtFkK1GcbOOecSZfHeLFavu3ZPOcxsCBtdyggl28FdOTTz5Jt9xyC6l1eJGPhxJGBOGU9IgXY4STHxmOKJyJFw5wlE5+mHiDc4ebQryfH9hChazR/CHepx8i21PtBTnYbqntEfGWnPUajdu73hSUISuUZrpWfl1HJAiQzLZt25xwkdoXy5cvd8oP9QNXxIuxydVgOBMvxill+BgnE29w7mpTiPeJTfOcyREiAUm8jeqQ7Z1+2n+v2eVQNvXmGoh32jCy1bnKTr4FG2l6Ml6RP30Ydd8QE3CUoRcrvTthc8oopzSB6HjNmjUFfmqzYayC8VAqPVcFon2z63z33XeFkYieGAH+KyBygCEJgluGasIPJn5EXEUngfMclDE7hl2oYmp0v00h3rarvtYn3gKH2XjQdf+0iBfkDTWzIlF2scNXL9jbUIoaBnck2zMdyAYCf/9JarnwU6Pxc6oP+pIwNMA4ECUhEI6xnRr04wDmw9jwg/xZ6fsXVUpjCqvpGvsx3Ii+FB7WYKUIouVkDQRMId4HV3+jT7y1q5Otdxvtv8cK1Mf0iBfk28buINz2YLPCxFu9YBNOQeqQu8KLP1Y12MXGDSl9tCJ6AsQEUpnemykCycpAhTfddJNwJ+jN9WaXhY9V/EAgmKMygYRBxiBlkDOn0EcAb2GYazg14mQNBEwh3sG/LNQnXl/0eCFqAOni76sX7SveokXIBuMJ5Yq3UwuyNW9AthtqEsQVxUqV1F9VK8gZNyl0bhHCBq+effv2FSa0iHX23Xff0ZYtW8QrmgyxA4Lq1q2b4+bWcsNnjen+rxd43cY4sUJXJvhhQD5s+zmFBwJwFIQ5hb4yJ2sgYArxzjiyq7AzHCnj9Zd4Qb4gYhBnk7rOxCvJefowoVUx5dB2gsI8XPxhUwGOUsaNG0cvvfSS0GtEaBU4hJHaCKJOFSGr87CJhhsa+RUrVqS9e/cWmll497KarBe+gNHn9u3bO/UXGg7Ib968uVM+H4QuAnCujznFmx4nayBgCvGeuXiBSs0a8d8qFYRoJPFiow2rWpDktXZ3izblhtv0YUKr4u/0cx6jjtUsXAZidQtLHzgPh4wMkR3gVhHiBOnrFe2CrEHg6oTov3C6PXnyZPWpoB7LyBcDBw506gdcBGI8Xbp0ccrng9BFQIqVoKPMyRoImEK8GOo9y7+iqBnD/yNfI4kXRP7eALJB3CBXqArijZo+jJovnRgQxOHmceLEiaJdrH6Tkpz9QiCGF/pUuXJlSk5ODkgffKn07bffFv166623nC6XYxkyZIhTPh+ELgKIH4d7EGGaOFkDAdOId3vi3xQdo4gsYTTxgnzbNxM3mCBfBfHCRy9cUQYy4ZUd7T733HOFmnnggQfEuRdffLHQuWBlPPvss6JPX331lVMXXn/9dZGP6A2cwgMBaKfg3oTzfU7WQMA04sVwe2+aTaWlyCEQxPv1ULJdUV7cZFLUABFH159nBRxtyI2hCQATYel6TzYqbeRxDq4IrZCkTwK9yATTp0+3Qje5DwYggLcyEC8843GyBgKmEi9iq9X+/n0qNrPAATpks4oNMM3vKANnOJ3vJJvU1XV3TcH5ojOG0zXz36ML2ZmmoP3yyy+LGxybdLD/V6YXXnhBnEMoFiskqNPhYdy5c6dTd2RYoFBx6OPUeT7QRADiL8y1WnVQszBnmoKAqcSLEZ3OOE/V5739H/l6QqIPNxc3jq1+TfdEXVAfyP3KuaPoZHqKKUCiEWhMSCcryqgGOAcldtz4eABgshnshB1u9OX06dNOXcGmIfKtsjJ36hwf+IQA9hYwpzCM4WQNBEwnXgz734upVP+HsYX9N2iRMJylwzotKspugaZVRpVXOmYk1f3+AzqVYY8qYCbUUlsA5rjqEOrSRSRMiuGsJFgJqm0QeyDQJSJjKBNU4vCQWmkjUNk//u49AnBmjznFBi8nayAQFOLF0DNzc6jewrGuV7CIUiFlto/c6brs9GEUNX04IdzPwC3f0cUcZ0IxC24YUyCeGm50ddh2EF7jxo3Fuffee8+sLhVqRyrUq3e5oUKHfpcoUaKQqKRQJZwRMgjgbQvzCq0bTtZAIGjEG3Nsj1sitd1eX9wwNpgVazk9V6x0S8wcQXf8NIF2Jp4KOrLw9gWzW/g8PXnypFN/YKAgz6md0zgVDODB7t27Ba4IvKlMcJiCBxRuAzmFNgJHzmfTnIMZ9PqWc9T3h6NiXktEV6CBqxPp9a3nxLmj54OzOAltZI3pfVCI93haMpWPfdM18fZrayfd0iUL+9xVEC425CAz3pUUfMJVTknv3r1F/7t3767MFt+l9/9evXoVOmdGxpIlS0TfEF5emRD2HMTbsmVLZTZ/DxEEsJ276d9Men5dMvVblUQ9lyXS48sSqMt8O/EWjy4vjpHXa0Ui9VuZSEN+TqYtZzLJeSs4RAYcwt0MOPFm5ebQin8O0rBdS6nV8q8IkSgKWbGpiNQ2ZoDdyTmMIQZ1cEnQVeaOIljGWS3BMYm0bFu/3tkP8D///EPR0dGC5DZu3Gh612FFB4J95plnnNqGHwrkw+8Ep9BCIP5iLr26OUWQKYhV+ddlgf1NpniZck75sky/VYn02pYUSriYG1qDDuHeBox44y+l0dAdPwofCRVmv0kIOqmpLiZJV6qWffPyf2a/d9/s8hrIdBef2mdZ+GGEACJDyHR1eHRpOdakSRPT/TiMGjVK9AufyiSjCyPyLqfQQWBf8mUCefZc7ky4kli7fn9czHex0mU1iRflcG3/VYl0IIXFD2bMvOHEi2jCXx7YSrAWKzlT5Z9BkqyrT+ldrGpFsk160SXxvrB9kRkY+dwGnOPUq1dP3PRqCzFsZMkQLFOmTPG5DV8ufPrpp0Wf1P4jZKyuDz/80Jdq+ZogILA/+TI9sdIuUpBEq/7sutDuca5YqWhd4pXXQPxwkMk34DNpKPFCU6Hj2mmF46u5IlrluVceIxG6HT4X3urtknRvWjSOLsX2UBcAAB++SURBVOVa/9cZlmFY9Wr5cZAOacz249ChQwfRJ8h6lalPnz4if9aswFv6Kdvl774hkHgpV6xSJWnqfXZdeFLMa7FSZdwSL+oYsCqRki6x2MG3WfHsKsOIF7Lcu5Z/4ZlurpJs5fcJz9n96kKu+7hG9GBZbvowISP+I+WMZyO0QCkZw0zL8Qz8/UJ3dsOGDab1FNoM+DGAdoMyyUi7cAjPydoIYDPs9a0puuIFJQk/9sPfYr6LliztEfH2Wp5Ib/ziuSc/ayNlzd4ZRrw9N8ZSmVkKJzgKonQp20U5yHcRew2kC+u0af9zudqFKCOUkis/DnA8bnaIHejvAmvo8ypT/fp29T1XsbqU5fl78BDYfjZLyHWVBKv3/bFFp+zEW6KUR8SLeiBy2BmXFbwBhnnLhhDv/JO/U3TsGy7J0iX59rjXTrplS5Nt/LMu63lozVSCHDnUEnz1guy0/DiYPZa5c+fSp59+WmjDD1E30Eco3HOyNgJD1yd7TKKPLTpdQLwlPb4G5PvyRvPM7a2NtvG985t4IWetPOf/XJKlS9Id3ZdsxYraZbtDH3VZT7V5bxO0JUIxIY4bvEOB2CDbtVpKT08XfYPRBydrI3DyQo7Hq10QaLcf/xFzW6R4Ca+IF5t2p9NyrA1GiPbOb+IVGgwxI10Spi7xTh5KtqsKAlLe39RlHVBHW3vmSIjCbO82tBdAvIhnpvbjEOyBHT58WPStbt26we4Kt+8Gge+PZFDvFa41GZRih26L7cEuixQr7hXx9lmRQD8eDZ5PETcwhPRpv4m37sIPXRKmLulCttvqFvGw22pcQbavX3JZT+sVk0IaaHQefhyaNbM7a4cer5USNvfwo4BIyZysjcDo7ee9ItDuS+zBLqOKFvPqOpD3uzvMdzRlbfSN6Z1fxAsXj6V93VBDhAhsphUvRrZ3+rkkXZB3o8WfGDPiINeCGG7w1QAdXrVnsGB2bc6cOWI+evToEcxucNtuELicm0/9VyV5RaDdf7IHu4wqUtSr60C82GRLzcpz0ys+7S0CfhHvvBO/U/nZbnwuaGk3fDqIbNGl7MTb9363pAviLTHzNcrJC48bANEd4CAnLU1fXg23kdjkCiQ5I5gndHZhqQYRA1xF3nPPPd7eQ1zeJAT2xGcJ3wpKMYLb70vjqcWrk6lIsRIEGW+L16bQ40vjvSJgWMUtOJxB2Xmht6lt0tR43YxfxDvqt1VUZEZBNAktgtXKg6pYg2vspHtLbbsqmVY5VV7Z2JF0LM06wSK9RlpxwTvvvCPGX7JkSTp06JDizH9fofOLN4LFixf/l+nHN4R/Wbp0KSG4Zbt27ahChQr2OcBbR8Ff+fL2sEmIlgGxCCdrIPBveg6N2emdeAGE3G7iOrqyYQvH/Mp5rnLj7dT2s9UekK8zQQ/dkExQY+PkPwJ+Ee/TWxd4tFp1kvMKx+ZFyFaxLNk+f97j6yvMfot2WMDlo/+QE0nixYMAEtRK/hAv/ELs27ePsJmHcPSIKgHxhnzw5CeiUHTs2FH4DYbRBJzkQKsB5x999FGCWTOn4CGQnp1HM/alOYwkeqic3+itdh+dd5jqdX6GIFrAXJYoV4maDnqP7nh5IpWqbNfhRmCBa+7uTB2n/+oBATv7gHh3+3k6dYG1Hfy5M/wi3oFb53tMnE7kO7In2Ub08OrairPfom0Jf/szVstcK4lXhgmCXq06eUO8MIT46aefaMSIEXTXXXc5yFMSLD7hDQ3nIFaAeEHtJ1i2D1/CCBGDa1q0aFEoXL0sx5++IZCbT5SRnS/+8F0rIX/tqUv01Bq7LFdNuN11CBibaM1e+IRKlrdrCkGLAQQMt5CSpGE+3LD3cCpaoqSYY1izNej2IsGfgyzjyWeP5Qn05e8XKPVy4Tcj/GAcPpdNu+OzhBEGHO8kZxYupzX2SMnzi3jf2LOColQiASeCNfBcudg36FBqYljMiyTejz/+WBAiCBh6vsqkR7zQt8UG3YQJEwi+fqUVmpJk8b1OnTpitYtyKA+HPZ4mWK4hPBHqwWr51Clr+Tr2dBxWKAe5KF7PP92TSoPWJhHMcXuvSBB/+P702iQatyuVtp7JJGycwdPY8M0pXpEgiLL1+z9QhetuFHOGeavWuBU9OGmzbj0dZ/5Gtdp0t4fUstmodJWr6Y7/feGF/Neuzvbk6kRafOyi0PeduT+dBq9LIqihwd8DzuFvwOpE6rvS/v3LPy4IUrbC3ASzD34R74wju6isPxZrXhBz8ZmvinBBwQTLqLYl8cbGxpJ0HQmiVSZJvHCygzhuAwcOFO4lESdNTbJVq1YlhGtHXevWrRNBN5V1+fIdq2gZpggiid9//92XaiL2GhDuj0czhBMbuFt0t4rEBhaI2F059XkHgRbI6cteVZvufH2qx/Xc/+lKuqKBPeI07qvKNzSlNh8v8/j6x5fZ5cBYAffScUup7DPKYazwM3EiNXLFFX4R74Hz8YRNr0CtcpX1Xv99+LgqVBJvZmYm1a5dWwSeVIZal8SLzbWrr77aQbbFihUTq9BBgwYJkQFkuepQ8kaxHVbh995rN+eGI59gOG03aixm1nM8NYeeW5ek6ZRcSUL+fIfjG6XIAJ7HcAwrNa/rXRovVrulKlW132dS/jvjN+/r0hGDFOrT8gThznL+4fQQdADg/93kF/Gi+arz3g448SKe2shfV/g/WovUoCRedAnkitVGo0aNHP4TlMQLB+UTJ06kHTt2eCUyMGK4WVlZBN1e9A9aGPPmzTOi2rCtY3tcliAUtVy2EPF4SlAa5e4eFUtlqtZ0JsmZOiS5NJ7gq8GT9rXkvyBzONnx5HpfysAs+ZPdqaQn7w7XG8Vv4h316yoqPcsHh+deiBlgpBEuqmS4kdTEizyICkBukMkiKYlXZATxH1bUw4cPF/2DdsS4ceOC2BvrNg1vXk94Ycrrnqic1bnaTVxLVW5qbidc+Hi+vrFLsYC9/B1Ur9PTXhGnQ3xRoAnjvfzXWQvC3ThBvhN/S7XuxAagZ34Tb3LWRRFtQikWMPJ7sRmvCufqARh70KrUIl5sYEHzAK/00Lm1EvFKoPCjIGXM0I5gXV+JDNE/6TluI0G4IyD1eam98Oi8Q07qYVAJg/ZC96VxmoTaefY+qt2uN0VF2fcDylS5miCaUNfv7vj+T1YUkv/e/8lyr+tx1w7Og3xX/x056ot+Ey9uvXF71/sedcLNyrdMzEg6kRZe7um0iBc4yo225557zpLEiz5iQ7B48eJi1YWgmJBRR3rKzyd6ZVMKGS1egHObpoPGEKID423IoR624Jgm+XlbXo8QJeHjPMgd2g5myH9BvikRonZmCPHm5udR86UThVmvkavd6JiRNOXQ9rB7rvWIF/JUOCPHBlqbNm3Ew2aU5ZqRIEJzQlq5oZ+pqZH1mqjGcuO/mYZvpN37/kKqUKuBQ6xQrck91H7SFk3CBUGifPlr7Y7sQdKi/OStuuX1SFcvXy3/lZt5Rsp/oWYHdbNISIYQL4CCyOHaBWOo+MzXDNlsA+k+v+2HsJwDPeLFYGFBhgdH/lmReNHPv/76i2rUqCH6ecsttxBC1kdqeuFnz52S6xGbzO8wdYewKJPzX/bqOnT3qNm6BKpVvtVo/fKyHV8/HfLfgnvUaPlvn5UJBAOMcE+GES+AiruURg1++Mh3j2UFYgeQ7iu7loRkpAlPbhhXxIvrpRYBHj6rEi/6Ces3GS4I3tYOHjzoyfDDqgx0UaGX6iuRyev0VpR66mGyPBzf4D5BBGGf1ck0NCdkv/Q+W3/4I1Wsc7NjgXBF/VvJCPkvxA3rT4e/+MpQ4sUThYgUA7d8R5DNRs0Y7tXqt9SsEVQ+9k1CKKFwTu6INy4uzuHExsrEizlKSUkRpsh4+BEtGVZykZQWeumUvBCRLY0XBg9lrrS/PcCHAizKOsfu1SZzWb5KgW63LD97n3Z5TVJ11pYo1CfNawprKmjJf0XfY/7yoi+F6/1oV/iLrgwnXvnQ7Uw8RXcv+5JKx4wUUYFdyX7Lxb4piHrojh+FyELWEa6fZ8+epT179gjS0hvjsWPHRBm1KbFe+WDmw4UlnO2AfEuVKmXJ0EaBwgeOwn0lLqnuBdzED1e9Ji5Xje0mrCF4FvO0vK/98vY6ufqW/h/+k/96pj+sbA8bezA7DvcUMOKVwB1PS6axf66nVsu/pCpzRlHRglVwyVkjqNb8MdR9/Syae/w3Ss9md3MSs1D8zM3NpWeffVaQAvz6Tp48ORSH4XWfn/ci6KQkGLW6V+nK1an5/77U9ZPwyNyDdnWyAvUwlHelTibbMfuzw9SdVKPFQ44fhuhq19J9Hy3x+ocJYY3CPQWceMMdQB6fMwJjx451PHjwlhYoc2bnVoN39NRq76JBgAxbjpwmXDZ6rB5Wxh792V15s4lWr73WHyyiirUbijEKyzcvdYihlqfjuC14E21wy0y8BgPK1RHNmDFDqMThlXjAgAEBjaIRbLyfKXDdqEdCWvkgUGDTfrIL9bAx31P5a29w/IhdfUc7wopSqz4r5iHcEPwAY5y68modWTKcBYV7YuIN9xkO0vjgH7hMmTLiwYOzd1dhjoLURUOafWWD9y4cpSaClsYCCOvqOx5wEG75a+rRPe/NF4SrNGywItmq+ySdrnf2crMNrjLDPTHxhvsMB3F88LZ25ZVXChK5/fbbKSEhIYi9CUzTn/2W6vUqVG5C6TmvqdthABWPrkCNBrxFsEZTE1qoHEMWjRVvp5g/vRrDO9udfVMHZuaCWysTb3DxD/vWoZ1x/fXXiwcQztmPHDkSVmOGzqm3erxFS9gDvepZfT363WF6ZM4Br8jKimRc+oqr7MQ76w+PxwKH6cuOXwyre0RrMEy8WqhwnqEIQH2uadOm4iHEZzhtuCH0DSIueEN8CLeDlaAvjmu8acessnf/X4zQRVaLTmDVJla8M3/3GJ8+KxMp+VKuofefFStj4rXirIRhnyDj7dq1a1hGsvhg13mvHORAzxWEBP1Xs8gxkO3IGG9Qe1O2A69oGCfMjJX5et97Lk8Q0ZTD8PYvNCQm3kKQcAYj4B0Cf1/IETHF9AhFnQ/zXjvxehdgUl2PVY5LVrAHR1WLR6Q1XkcPI1lAzHAqLTLCATHxeveMcWlGQBOBb/664DH5Fitd1k683x/3aCVoFYLV60fJilXEeB6Zvd9pPDJKhich5EG6MfvTNbENx0wm3nCcVR6T6QggQvDLG5M9CvhYvMAgoouOX109grNqfqmKds0VWOQp+xhd7RpByA9P2+OUryyD73AHOXJrSkSF/2HiNf0R5QbDFYFzmXnCz0AvN5tt0rF5l/lHXRKSmqCseiydpKsNJWAyDJHKw9N2644TpDtsUwplZIe7rZrzXc/E64wHHzECfiFwPiuPhruJRgEdXRBSl/lHdAnJTrLGeBELNGHrGUpEV69lJ95vd+mOc/S2c5SZE1mkixuMidevx4wvZgQKI5CTl089l+n76C1RtqIgJOjrBpoUzahfz1Ci7FXXiXG6MnWOlM009V3CxKtGhI8ZAQMQ6OMi2nCJcgXEO0+LeOUqV356pyNsBtGq29AzlCh7Ve0C4t2h+wMDjZBITEy8kTjrPOaAI4BdejVByWPpPAbRg2VeKH/qGUogbBFEKh2+2a47zpNMvAG/F7kBRiBiEEAIGz0y1TM40Ctv9Xw9Q4lyNeoK4n1oyjZdLJh4I+aR4IEyAoFHwCXx6hgcWJ1gtfsXT3qGEuVq2n10PPT1L7rEi5h1kZhY1BCJs85jDjgCrhzn6BkcaBOb9WW8eoYS5WrWs694v9YPM3+ciTfg9yI3wAhEDAL9XUQe1jM4CFXi1TOUgC9hyHjbT2biVd/4vOJVI8LHjIABCLgk3srVBCF56yDcqsSsZyghI2i0n6QfaePY+WwD0A69Kph4Q2/OuMchgMAAFytePb1XqxKru37pGUqUv7a++IF5cNJmXRnvUSbeELibuYuMQIgg8ORqfa0GPb1XdwRn1fN6hhIVajWwE+9Xm5h4Vfctr3hVgPAhI2AEAq421/T0Xq1KrO76pWcoUeG6G+3E++VGTeJFDLld8VlGwB1ydTDxhtyUcYetjEB+PtHM/enUw4XJsJ7eqzuCs+p5PUOJitfdJIj3gS83aBIvxgNDkz+TLlt5SgPSNybegMDKlUYiAnn5RB/vTiVXOrwgGz29V21itb7psJ6hRMXaDe3E+8V6XeKV5LsnIbJWvky8kcgQPOaAIDDlrwtuSVcQb9WagpA8cRCuTcbW0u3VM5SoWOdmO/F+/rNL4sUY8WMVSX4bmHgD8ghypZGGwPa4LOrnwkxYSaB6eq/KMqH0Xc9QolLdWwTxtpu4zi3xPr48gYb8nEzZeG2IgMTEGwGTzEMMLALwJ+tKi0FNonp6r+pyoXKsZyhRqW6jAuJd6554C1a9Px7LCOxkWaR2Jl6LTAR3I3QRAFm4k+sqSVRP71VZJpS+6xlKVLq+sZ14J6zxiHgxZhieRMKql4k3dJ937rkFEMCL8dNrkjwmFpCLnt6r9clWe6Ov08zf6eFvd1G3xf864VC5XhNBvG0/W+2U72qcIN5fzmRaYGYD2wUm3sDiy7WHOQJw8tJvlbfE69pBePclZzwIC2StDTYtMvWFeFHP2N2pYX7XcOifsJ9gHmBgEVhy/CL1cRPcUk1Kenqvstytgz8gRKloOmgMgYRlfqh9Vr6hqX3FO36VV2MYuCYxsJNmgdp5xWuBSeAuhC4C439N9YpUQJ56eq+SWGve1UkQFjx7wez23jHfe92GrCuYn1fUv1WM4/5PV3rV/57LEyj5Um7o3hQe9JyJ1wOQuAgjoIfAG1vPeUUqgngLHIS3GfeT7rV3j4p1yIJBwNWa3EOunM0Ek2C12u48ex+VvqK6IN7GA0fpjlPrWuQNWJ1Iy09cpNww1S5j4tV7ojifEfAAgVc3e0+8d/9fDCH8T9GSpalh7+H02KLTmsSEzSqIG4pHlxcEVqRYcarT/gl6ZO5BzfJ6JGZmvrrPGCN+OKo2vptcmQ7r9fGVjcn0W0L4mRQz8XrwcHERRkAPgVHbzntNglgN1mjRXhASSAnqZS1HTtOtB0Ex63V+hqKKFBXXWFX+e+/7C0m6ghSr9MatqGGf10hG3IiKKkK12nQnjF+PaPXy39txnk6nhU+YICZevSeK8xkBDxD4+o8LXpOIJJfWHywi6c8ARHVFg9tIXx4aLyI5VL+tjYOwYTHW6u05Prcv++HvZ4epO+iauzv/168adanV6NmOfj363WFq0O1Fwood4yweXYEaDXiLuv34j6OMJ33otTyBZuxLo4xs3+QPl3LyLSO6YOL14OHiIoyAHgLrT2eSKxeQ7gil+9I4uuN/X5AMB+RYFcbu1SUlLfmvqygP7vrg6/muC08KUUmR4iUEoRYrFS2O9QgV0YaVBA3tjjtfn6o7Tr1+DVydpCv/zcnLp/3Jl2nB4Qwas+M8PfdzMvUt0DrpvSKBeiyz/8HScPimFPrqzwu04Z9MSjR5M4+JV++J4nxGwAMEsPved4W+03M98lDnd114QkViZbyW/0Ic0WX+Ea+JTN0Xt8dL4wVhSveWtqgor0QI0NKQvnqxAjZC/nsgJZs+3ZNKfVcm0IBVSdR7ued6zvCxgTl8cX0yLTl2kdIu53kw8/4VYeL1Dz++mhGg1zanGEZ26td2kBtWxHpkaLb8t92ENVTlxtsdYgUYSdz/yQrd/un1G/rJzV74hEoWhLqXK/1HZu/3ui6YawuTbS/IVq9fT6xMECT87d70gBIwEy8TByPgJwK74z33TKb3wKvzW7//A0lH4mJVeEtLesCFe0WIGqrfep+DEO3y37lek5i6H/IYmhRigy+qiGgDceNAnBCVyDK+fBol//WlbVfXwCim/8pEgigpEImJNxCocp0RhQC2el7bkkJQ/Hf1MHt7Tsp/3WkFIISOrNto+a9DPaxMOUG42CATIo0Fxxxtyrb9+YT89+o72jl+OHyV//rTB61rsZL+ZE+q4Y57mHgjiiJ4sIFC4GxGrlceyrQecr08yG2FVoBjE8uN/PfHf6hR/zepWOmyDrJ80EXASb12IYuVnsew6gYxdpi601DCVbct5L8FQTL9kf+q6/XnGOGJRm5NIbj/NCox8RqFJNcT8QjsiMsKGPmCODp8s91JKwAhhDyR/1Zr3MorskQ7ytUnTJzNVFvzRf6La9qMW0p3vDyRbnv+I2rx2hTdH4mOM36je96ZR5Cn6xFyl/lHRRnpWQ2bb6O3nSOj/LQz8UY8XTAARiKw6Z9MEcBR74E2Ir+Q/LfRXfSAi7hmaneNen1Qq4c59G1V7h71rjc631P57+1DP6NSlao6xBRYKcu/Kjc1L2QxBydEOH9Tz//pEm/b8atEmepNWzvKQOww71C6IbcLE68hMHIljMB/COxPziZ42DJCzUyPzDyV/+pd75S/NN6uS1xAXlLDwBcLM6d6FbJnf/ILbxxeT1J00rD3q4IgYVYNIr1v7I8EzYu73ppJNVs+bD9XphzJlSv64Svx4lqIHc5k+O/Ah4n3v+eFvzEChiFwMSefpu1LF+QL3VJ3xNNzeSL19NK9JOosLP91bcSg7gcIyQj1MBAS/nq5GQN8F/dekehxfDplf6X8FypoGPf9nywn/EiUKFeJHvp6qybGjZ78P0G+2KyTLjb9IV7ME/SF/U1MvP4iyNczAi4QuHA5j346dpGGb04RhIMIC/C8BesrfIc11eB1STRtbzqdvJBDR89n01u/eO94Ry3/LXtVbZdWYZ1j/hIOd0BceO2GepiQFy/VjjKhJEDld/Qd4hVsO51IzaE5BzOEhgdUsWS5XssTafC6ZEFYW85kUlZuvviDdVkfL41PIDZ58MuNom7pPvPWwR862pJtOj6XxpP0C9xy5LeinD/Ei3qhaoYfVn8SE68/6PG1jIAXCMDF4b/puQQrq71Jl+nUhRzNBxiP9PazWfT8z8n6hKLzGg9HNU5WYSr5r556WNfvj3vUFkxuQT5Y3c45mO73Tn/SpVz68vf//F3I+h3EqTNOiFqE17aoKHp03mGXfW/67Pvix6XOg31EOX+Jd8CqRNoVl+XFzBcuysRbGBPOYQQsgQBWhspVocekJK3CKlYRhCNltvCLoFYPQ6w0dySnPj92VyolXPRfzqkEGf4VvLEAhGYCVuqw7FP3T31830dLRNkrGjRzIt7abXtRm4+Xaf5hww71KzfXZL09lyWKeVH239vvTLzeIsblGQGTEUjOzBOrQk+JVxIEVoIwdpBewYoULynIBK4bIS+V5Tz9hG/cPxID5xs3P5+E2OKZte5j2EGLA8QI6z53/cfmHMrCmg9l5YoXee7+tIgXdcArnT+Jidcf9PhaRsBEBCD/fdOHiBfYeLq2dVdq+sx7PsVx678qQdcbWCCGr17paxFr+8lbC35EbnBLvA6Srt3QiXivvuMBuv2lzzT/bur5iqhfj3i/+SvNr6Ez8foFH1/MCJiLAOS/7+7w3vm6Fnl5kodd/H8yguOAXC3/VfYXzoGwWoWu8eNuNgThGxhlJYnKFa+3eryyfWhlLD5+0a+JZ+L1Cz6+mBEwH4FVf18KuJGGJBmowvm3f+8/Pi9t1N5kjK52rSBUd76Ib+z+kih34+MvOa14fSVeuJ2ErrY/iYnXH/T4WkYgCAhAbav/KvdyUEme/nxCtS3YacWJS5qm2A26DxWEWrfDAF1xA7Q1SlWuJspJNTR/V7xQlfM3CCcTb7DvKm6fEfASAWxCDVydSEqvZP6Qq961MJFd+fclL3tnfHGE+hH+dlWqZZ1j9wrjCWhtNHtxfCHyhXN5yHEhZrj2nkcd5/0hXrsaXYbfg2Ti9RtCroARMB+BuYcyAi5ugMlzenbgozF4gt4PRzM0yRd+K6QXNsSsg/ig8cDRdH3HgY6VLvLh90H+wPhDvE+uSvQ55ptynEy8SjT4OyMQIgjAIk5rFSjJxd/PPisThcmzVeDAq/2wTSkEKzj12OBlrNZ93ah4gc9gqSIG6z0E1Xxs0Wmna24b8jEVLVGKbu77ulO+sl74e0CZq5s/6CgDvOGBzojExGsEilwHIxAEBJYcy/Ar0KaSaNTfEQzS12i+gYIC+sxPrUnSdTgPXwydZv4uojEjYoZ6TP4cIy7b3IP+ixgkNky8Egn+ZARCDAHIerH55a2/A3cEBDnmn0mBM5TwB+a4jFyCgUVvjZWvu3H5er7fqgSK2W+MO0g5diZeiQR/MgIhiABWpYiOC2c7vhKL8jqxoXYy+BtqrqYiNSuP3th6LqCiFmACS0Hg8fMp4+OuMfG6mmE+xwiEAAIIR/7q5hS/N9uw0l17ytqkK6cDq/2lxy8KYoS3MOWPhxHfIVp4fcs5Q3zvyj4rP5l4lWjwd0YgRBHIycunWfvT6YkViboyUD1CQkjz539OEi4pQ2342GSciXGv8s3HrxITbNxhhTt8Uwr9mmDMJpoenky8eshwPiMQggj8k55D43anCp+xcDquJBbld5AM/AFDXgoDBRB3KCf4d9j4TyaN2gaZd4IYm7sIIBAl9F9td+A+aG0STd9n94lsBg5MvGagzG0wAiYjgJXg+tOZNP7XVHp5Ywo9vSaJ4EcWjsvf+OWccFh+MCWb8Moebik7L58OncsmmFbDmQ18W4zYnEIvbUim/21KoTd/OSdCts8/lCH8HsMnhNmJiddsxLk9RoARiHgEmHgj/hZgABgBRsBsBJh4zUac22MEGIGIR4CJN+JvAQaAEWAEzEaAiddsxLk9RoARiHgEmHgj/hZgABgBRsBsBJh4zUac22MEGIGIR4CJN+JvAQaAEWAEzEaAiddsxLk9RoARiHgE/h+iX2DVgWhk5QAAAABJRU5ErkJggg==" } }, "cell_type": "markdown", "metadata": {}, "source": [ "This one was inspired by a conversation that happened at the 2020 RDKit (virtual) UGM. \n", "\n", "During Dominique Sydow's presentation she showed some pictures of molecules with some regions of the molecule highlighted (in her case to indicate which kinase pocket they interact with). Dominique had created the images by hand, but I wanted to explore what's possible using the 2020.09 RDKit release.\n", "\n", "What this post is going to demonstrate is doing R-group decomposition (RGD) on a set of molecules that share a common scaffold, generating coordinates for those molecules that are aligned to the scaffold, and generating images of the molecules where the R groups are colored to make them easy to pick out.\n", "\n", "The final images we create will look like this:\n", "\n", "![image.png](attachment:image.png)\n", "\n", "The rest of this post will go through the steps to create images like this.\n", "\n", "Let's get started" ] }, { "cell_type": "code", "execution_count": 1, "metadata": {}, "outputs": [ { "name": "stdout", "output_type": "stream", "text": [ "2021.03.4\n" ] } ], "source": [ "from rdkit import Chem\n", "from rdkit.Chem import Draw\n", "from rdkit.Chem.Draw import IPythonConsole\n", "IPythonConsole.molSize=(450,350)\n", "from rdkit.Chem import rdRGroupDecomposition\n", "from rdkit.Chem import rdqueries\n", "from rdkit.Chem import rdDepictor\n", "from rdkit.Chem.Draw import rdMolDraw2D\n", "from rdkit import Geometry\n", "rdDepictor.SetPreferCoordGen(True)\n", "import pandas as pd\n", "\n", "from IPython.display import SVG,Image\n", "from ipywidgets import interact\n", "\n", "import rdkit\n", "print(rdkit.__version__)" ] }, { "cell_type": "markdown", "metadata": {}, "source": [ "Start by reading in the data we will use. This is a collection of ChEMBL compounds with Ki data measured for CDK2. The dataset includes compounds from a number of different documents and, since these are medchem papers, many of the documents contain groups of compounds that share a common scaffold." ] }, { "cell_type": "code", "execution_count": 2, "metadata": { "scrolled": true }, "outputs": [ { "data": { "text/html": [ "
\n", " | assay_id | \n", "doc_id | \n", "description | \n", "assay_organism | \n", "assay_chembl_id | \n", "aidx | \n", "pref_name | \n", "activity_id | \n", "molregno | \n", "standard_relation | \n", "... | \n", "src_id (#1) | \n", "type | \n", "relation | \n", "value | \n", "units | \n", "text_value | \n", "standard_text_value | \n", "standard_inchi_key | \n", "canonical_smiles | \n", "compound_chembl_id | \n", "
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "265814 | \n", "68026 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "20.00 | \n", "uM | \n", "NaN | \n", "NaN | \n", "RPXWUUDZINQPTJ-UHFFFAOYSA-N | \n", "CNc1nccc(n1)c2sc(C)nc2C | \n", "CHEMBL46474 | \n", "
1 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "265817 | \n", "67880 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.14 | \n", "uM | \n", "NaN | \n", "NaN | \n", "GDZTURHUKDAJGD-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(Nc3ccc(O)cc3)n2 | \n", "CHEMBL442957 | \n", "
2 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267078 | \n", "67751 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "6.50 | \n", "uM | \n", "NaN | \n", "NaN | \n", "CTFDMGIBHFQWKB-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(N)n2 | \n", "CHEMBL47302 | \n", "
3 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267081 | \n", "67782 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "1.20 | \n", "uM | \n", "NaN | \n", "NaN | \n", "HOKDXVAONYXHJK-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(Nc3ccccc3F)n2 | \n", "CHEMBL297447 | \n", "
4 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267084 | \n", "67961 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.11 | \n", "uM | \n", "NaN | \n", "NaN | \n", "XNKSRGHGPSHYIW-UHFFFAOYSA-N | \n", "CNc1nc(C)c(s1)c2ccnc(Nc3cccc(O)c3)n2 | \n", "CHEMBL44119 | \n", "
5 rows × 28 columns
\n", "\n", " | assay_id | \n", "doc_id | \n", "description | \n", "assay_organism | \n", "assay_chembl_id | \n", "aidx | \n", "pref_name | \n", "activity_id | \n", "molregno | \n", "standard_relation | \n", "... | \n", "src_id (#1) | \n", "type | \n", "relation | \n", "value | \n", "units | \n", "text_value | \n", "standard_text_value | \n", "standard_inchi_key | \n", "canonical_smiles | \n", "compound_chembl_id | \n", "
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
47 | \n", "302524 | \n", "21080 | \n", "Binding affinity for human cyclin-dependent ki... | \n", "Homo sapiens | \n", "CHEMBL827377 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "1438958 | \n", "305637 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "19.95 | \n", "uM | \n", "NaN | \n", "NaN | \n", "TWQUOUJLNRGSRZ-UHFFFAOYSA-N | \n", "Cc1ccc2c(c3ccnc(Nc4cccc(c4)C(F)(F)F)n3)c(nn2n1... | \n", "CHEMBL182493 | \n", "
48 | \n", "302524 | \n", "21080 | \n", "Binding affinity for human cyclin-dependent ki... | \n", "Homo sapiens | \n", "CHEMBL827377 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "1438962 | \n", "305651 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "19.95 | \n", "uM | \n", "NaN | \n", "NaN | \n", "CYHPFZLFUXOCJJ-UHFFFAOYSA-N | \n", "Cc1ccc2c(c3ccnc(Nc4ccc(F)c(F)c4)n3)c(nn2n1)c5c... | \n", "CHEMBL182326 | \n", "
49 | \n", "302524 | \n", "21080 | \n", "Binding affinity for human cyclin-dependent ki... | \n", "Homo sapiens | \n", "CHEMBL827377 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "1439061 | \n", "305664 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "19.95 | \n", "uM | \n", "NaN | \n", "NaN | \n", "MYSOMHSTKVRJRA-UHFFFAOYSA-N | \n", "Cc1ccc2c(c3ccnc(Nc4ccc5OCCOc5c4)n3)c(nn2n1)c6c... | \n", "CHEMBL183064 | \n", "
50 | \n", "302524 | \n", "21080 | \n", "Binding affinity for human cyclin-dependent ki... | \n", "Homo sapiens | \n", "CHEMBL827377 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "1439063 | \n", "305674 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "19.95 | \n", "uM | \n", "NaN | \n", "NaN | \n", "VUGNSTAXWJUVEZ-UHFFFAOYSA-N | \n", "Cc1ccc2c(c3ccnc(Nc4ccc(Cl)c(c4)C(F)(F)F)n3)c(n... | \n", "CHEMBL361038 | \n", "
51 | \n", "302524 | \n", "21080 | \n", "Binding affinity for human cyclin-dependent ki... | \n", "Homo sapiens | \n", "CHEMBL827377 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "1439065 | \n", "305687 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "3.98 | \n", "uM | \n", "NaN | \n", "NaN | \n", "BWBMBCPGRIOUNV-UHFFFAOYSA-N | \n", "C1CC1c2nn3ncccc3c2c4ccnc(Nc5ccccc5)n4 | \n", "CHEMBL362296 | \n", "
5 rows × 28 columns
\n", "\n", " | assay_id | \n", "doc_id | \n", "description | \n", "assay_organism | \n", "assay_chembl_id | \n", "aidx | \n", "pref_name | \n", "activity_id | \n", "molregno | \n", "standard_relation | \n", "... | \n", "src_id (#1) | \n", "type | \n", "relation | \n", "value | \n", "units | \n", "text_value | \n", "standard_text_value | \n", "standard_inchi_key | \n", "canonical_smiles | \n", "compound_chembl_id | \n", "
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
0 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "265814 | \n", "68026 | \n", "> | \n", "... | \n", "1 | \n", "Ki | \n", "> | \n", "20.00 | \n", "uM | \n", "NaN | \n", "NaN | \n", "RPXWUUDZINQPTJ-UHFFFAOYSA-N | \n", "CNc1nccc(n1)c2sc(C)nc2C | \n", "CHEMBL46474 | \n", "
1 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "265817 | \n", "67880 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.14 | \n", "uM | \n", "NaN | \n", "NaN | \n", "GDZTURHUKDAJGD-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(Nc3ccc(O)cc3)n2 | \n", "CHEMBL442957 | \n", "
2 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267078 | \n", "67751 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "6.50 | \n", "uM | \n", "NaN | \n", "NaN | \n", "CTFDMGIBHFQWKB-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(N)n2 | \n", "CHEMBL47302 | \n", "
3 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267081 | \n", "67782 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "1.20 | \n", "uM | \n", "NaN | \n", "NaN | \n", "HOKDXVAONYXHJK-UHFFFAOYSA-N | \n", "Cc1nc(C)c(s1)c2ccnc(Nc3ccccc3F)n2 | \n", "CHEMBL297447 | \n", "
4 | \n", "50641 | \n", "17759 | \n", "Inhibitory activity against human CDK2 (Cyclin... | \n", "NaN | \n", "CHEMBL658107 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "267084 | \n", "67961 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.11 | \n", "uM | \n", "NaN | \n", "NaN | \n", "XNKSRGHGPSHYIW-UHFFFAOYSA-N | \n", "CNc1nc(C)c(s1)c2ccnc(Nc3cccc(O)c3)n2 | \n", "CHEMBL44119 | \n", "
5 rows × 28 columns
\n", "\n", " | assay_id | \n", "doc_id | \n", "description | \n", "assay_organism | \n", "assay_chembl_id | \n", "aidx | \n", "pref_name | \n", "activity_id | \n", "molregno | \n", "standard_relation | \n", "... | \n", "src_id (#1) | \n", "type | \n", "relation | \n", "value | \n", "units | \n", "text_value | \n", "standard_text_value | \n", "standard_inchi_key | \n", "canonical_smiles | \n", "compound_chembl_id | \n", "
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1129 | \n", "1281340 | \n", "76402 | \n", "Displacement of B-Alexa-Fluor647 from CDK2 (un... | \n", "Homo sapiens | \n", "CHEMBL3101313 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "13859835 | \n", "1610535 | \n", "< | \n", "... | \n", "1 | \n", "Ki | \n", "< | \n", "0.10 | \n", "uM | \n", "NaN | \n", "NaN | \n", "USOUMMYIFYDJEI-ZZTDINLMSA-N | \n", "COC[C@H](Cc1ccc(O)cc1)NC(=O)c2cc(C(=O)O)c3cc(\\... | \n", "CHEMBL3099753 | \n", "
1130 | \n", "1281340 | \n", "76402 | \n", "Displacement of B-Alexa-Fluor647 from CDK2 (un... | \n", "Homo sapiens | \n", "CHEMBL3101313 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "13859836 | \n", "1610534 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.10 | \n", "uM | \n", "NaN | \n", "NaN | \n", "DLJWCYCMLMVSML-FQEVSTJZSA-N | \n", "COC[C@H](Cc1ccc(O)cc1)NC(=O)c2cc(C(=O)O)c3cc(c... | \n", "CHEMBL3099752 | \n", "
1131 | \n", "1281340 | \n", "76402 | \n", "Displacement of B-Alexa-Fluor647 from CDK2 (un... | \n", "Homo sapiens | \n", "CHEMBL3101313 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "13859837 | \n", "1610533 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.16 | \n", "uM | \n", "NaN | \n", "NaN | \n", "BHBDKGIDYKROMY-BAJJQUEBSA-N | \n", "CN(C)C(=O)[C@H](Cc1ccc(O)cc1)NC(=O)c2cc(C(=O)O... | \n", "CHEMBL3099751 | \n", "
1132 | \n", "1281340 | \n", "76402 | \n", "Displacement of B-Alexa-Fluor647 from CDK2 (un... | \n", "Homo sapiens | \n", "CHEMBL3101313 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "13859838 | \n", "1610532 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.10 | \n", "uM | \n", "NaN | \n", "NaN | \n", "IYRLCOILNQBJEJ-ZNOKPGKASA-N | \n", "CNC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)c2cc(C(=O)O)c3... | \n", "CHEMBL3099750 | \n", "
1133 | \n", "1281340 | \n", "76402 | \n", "Displacement of B-Alexa-Fluor647 from CDK2 (un... | \n", "Homo sapiens | \n", "CHEMBL3101313 | \n", "CLD0 | \n", "Cyclin-dependent kinase 2 | \n", "13859839 | \n", "1610531 | \n", "= | \n", "... | \n", "1 | \n", "Ki | \n", "= | \n", "0.30 | \n", "uM | \n", "NaN | \n", "NaN | \n", "DDIHZTFUIFPFOO-OAQYLSRUSA-N | \n", "CCC[C@H](Cc1ccc(O)cc1)NC(=O)c2cc(C(=O)O)c3cc(c... | \n", "CHEMBL3099749 | \n", "
5 rows × 28 columns
\n", "