2pr3: Difference between revisions
New page: left|200px<br /> <applet load="2pr3" size="450" color="white" frame="true" align="right" spinBox="true" caption="2pr3, resolution 1.5Å" /> '''Factor XA inhibitor'... |
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[[Image:2pr3. | [[Image:2pr3.jpg|left|200px]]<br /><applet load="2pr3" size="350" color="white" frame="true" align="right" spinBox="true" | ||
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caption="2pr3, resolution 1.5Å" /> | caption="2pr3, resolution 1.5Å" /> | ||
'''Factor XA inhibitor'''<br /> | '''Factor XA inhibitor'''<br /> | ||
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==Overview== | ==Overview== | ||
A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor, Xa inhibitors using structure-based drug design. This series consisted of, a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline, scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in, an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) =, 0.38 nM), which was shown to be efficacious in a canine electrolytic model, of thrombosis with minimal bleeding. | A novel series of pyrrolidine-1,2-dicarboxamides was discovered as factor, Xa inhibitors using structure-based drug design. This series consisted of, a neutral 4-chlorophenylurea P1, a biphenylsulfonamide P4 and a D-proline, scaffold (1, IC(50) = 18 nM). Optimization of the initial hit resulted in, an orally bioavailable, subnanomolar inhibitor of factor Xa (13, IC(50) =, 0.38 nM), which was shown to be efficacious in a canine electrolytic model, of thrombosis with minimal bleeding. | ||
==About this Structure== | ==About this Structure== | ||
2PR3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with CA and 237 as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http:// | 2PR3 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=CA:'>CA</scene> and <scene name='pdbligand=237:'>237</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Coagulation_factor_Xa Coagulation factor Xa], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.6 3.4.21.6] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PR3 OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: fxa coagulation factor inhibitor]] | [[Category: fxa coagulation factor inhibitor]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 13:37:29 2008'' | ||
