2p3t: Difference between revisions
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|PDB= 2p3t |SIZE=350|CAPTION= <scene name='initialview01'>2p3t</scene>, resolution 1.92Å | |PDB= 2p3t |SIZE=350|CAPTION= <scene name='initialview01'>2p3t</scene>, resolution 1.92Å | ||
|SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+B+501'>AC1</scene>, <scene name='pdbsite=AC2:Cl+Binding+Site+For+Residue+B+502'>AC2</scene> and <scene name='pdbsite=AC3:993+Binding+Site+For+Residue+B+500'>AC3</scene> | |SITE= <scene name='pdbsite=AC1:Ca+Binding+Site+For+Residue+B+501'>AC1</scene>, <scene name='pdbsite=AC2:Cl+Binding+Site+For+Residue+B+502'>AC2</scene> and <scene name='pdbsite=AC3:993+Binding+Site+For+Residue+B+500'>AC3</scene> | ||
|LIGAND= <scene name='pdbligand= | |LIGAND= <scene name='pdbligand=993:3-CHLORO-4-(2-METHYLAMINO-IMIDAZOL-1-YLMETHYL)-THIOPHENE-2-CARBOXYLIC+ACID+[4-CHLORO-2-(5-CHLORO-PYRIDIN-2-YLCARBAMOYL)-6-METHOXY-PHENYL]-AMIDE'>993</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene> | ||
|ACTIVITY= [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] | |ACTIVITY= <span class='plainlinks'>[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] </span> | ||
|GENE= | |GENE= | ||
|DOMAIN= | |||
|RELATEDENTRY=[[1fjs|1FJS]], [[1mq5|1MQ5]], [[1mq6|1MQ6]], [[1ezq|1EZQ]], [[1f0s|1F0S]], [[1f0r|1F0R]], [[2p3u|2P3U]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p3t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p3t OCA], [http://www.ebi.ac.uk/pdbsum/2p3t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p3t RCSB]</span> | |||
}} | }} | ||
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[[Category: Adler, M.]] | [[Category: Adler, M.]] | ||
[[Category: Whitlow, M.]] | [[Category: Whitlow, M.]] | ||
[[Category: blood clotting]] | [[Category: blood clotting]] | ||
[[Category: coagulation cofactor]] | [[Category: coagulation cofactor]] | ||
| Line 34: | Line 34: | ||
[[Category: protein inhibitor complex]] | [[Category: protein inhibitor complex]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 04:28:42 2008'' | ||
Revision as of 01:28, 31 March 2008
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| 2p3t, resolution 1.92Å | |||||||||||||
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| Sites: | AC1, AC2 and AC3 | ||||||||||||
| Ligands: | 993, CA, CL | ||||||||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||||||||
| Related: | 1FJS, 1MQ5, 1MQ6, 1EZQ, 1F0S, 1F0R, 2P3U
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
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
Overview
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 Structure
2P3T is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
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
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