2P3T
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
Summary for 2P3T
| Entry DOI | 10.2210/pdb2p3t/pdb |
| Related | 1EZQ 1F0R 1F0S 1FJS 1MQ5 1MQ6 2P3U |
| Descriptor | Coagulation factor X, CALCIUM ION, CHLORIDE ION, ... (6 entities in total) |
| Functional Keywords | protein inhibitor complex, nonamidine, coagulation cofactor, protease, blood clotting |
| Biological source | Homo sapiens (human) More |
| Cellular location | Secreted: P00742 P00742 |
| Total number of polymer chains | 2 |
| Total formula weight | 32576.62 |
| Authors | Adler, M.,Whitlow, M. (deposition date: 2007-03-09, release date: 2008-01-22, Last modification date: 2024-11-06) |
| Primary citation | Ye, B.,Arnaiz, D.O.,Chou, Y.L.,Griedel, B.D.,Karanjawala, R.,Lee, W.,Morrissey, M.M.,Sacchi, K.L.,Sakata, S.T.,Shaw, K.J.,Wu, S.C.,Zhao, Z.,Adler, M.,Cheeseman, S.,Dole, W.P.,Ewing, J.,Fitch, R.,Lentz, D.,Liang, A.,Light, D.,Morser, J.,Post, J.,Rumennik, G.,Subramanyam, B.,Sullivan, M.E.,Vergona, R.,Walters, J.,Wang, Y.X.,White, K.A.,Whitlow, M.,Kochanny, M.J. Thiophene-anthranilamides as highly potent and orally available factor xa inhibitors. J.Med.Chem., 50:2967-2980, 2007 Cited by PubMed Abstract: 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. PubMed: 17536795DOI: 10.1021/jm070125f PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.92 Å) |
Structure validation
Download full validation report
