2p3t: Difference between revisions
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'''Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide''' | '''Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide''' | ||
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[[Category: Adler, M.]] | [[Category: Adler, M.]] | ||
[[Category: Whitlow, M.]] | [[Category: Whitlow, M.]] | ||
[[Category: | [[Category: Blood clotting]] | ||
[[Category: | [[Category: Coagulation cofactor]] | ||
[[Category: | [[Category: Nonamidine]] | ||
[[Category: | [[Category: Protease]] | ||
[[Category: | [[Category: Protein inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 12:17:22 2008'' | |||
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Revision as of 12:17, 4 May 2008
Crystal structure of human factor XA complexed with 3-Chloro-4-(2-methylamino-imidazol-1-ylmethyl)-thiophene-2-carboxylic acid [4-chloro-2-(5-chloro-pyridin-2-ylcarbamoyl)-6-methoxy-phenyl]-amide
OverviewOverview
There remains a high unmet medical need for a safe oral therapy for thrombotic disorders. The serine protease factor Xa (fXa), with its central role in the coagulation cascade, is among the more promising targets for anticoagulant therapy and has been the subject of intensive drug discovery efforts. Investigation of a hit from high-throughput screening identified a series of thiophene-substituted anthranilamides as potent nonamidine fXa inhibitors. Lead optimization by incorporation of hydrophilic groups led to the discovery of compounds with picomolar inhibitory potency and micromolar in vitro anticoagulant activity. Based on their high potency, selectivity, oral pharmacokinetics, and efficacy in a rat venous stasis model of thrombosis, compounds ZK 814048 (10b), ZK 810388 (13a), and ZK 813039 (17m) were advanced into development.
About this StructureAbout this Structure
2P3T is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors(1)., Ye B, Arnaiz DO, Chou YL, Griedel BD, Karanjawala R, Lee W, Morrissey MM, Sacchi KL, Sakata ST, Shaw KJ, Wu SC, Zhao Z, Adler M, Cheeseman S, Dole WP, Ewing J, Fitch R, Lentz D, Liang A, Light D, Morser J, Post J, Rumennik G, Subramanyam B, Sullivan ME, Vergona R, Walters J, Wang YX, White KA, Whitlow M, Kochanny MJ, J Med Chem. 2007 Jun 28;50(13):2967-80. Epub 2007 May 31. PMID:17536795 Page seeded by OCA on Sun May 4 12:17:22 2008