2p95: Difference between revisions
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|PDB= 2p95 |SIZE=350|CAPTION= <scene name='initialview01'>2p95</scene>, resolution 2.20Å | |PDB= 2p95 |SIZE=350|CAPTION= <scene name='initialview01'>2p95</scene>, resolution 2.20Å | ||
|SITE= | |SITE= | ||
|LIGAND= <scene name='pdbligand=ME5:5-CHLORO-N-((1R,2S)-2-(4-(2-OXOPYRIDIN-1(2H)-YL)BENZAMIDO) CYCLOPENTYL)THIOPHENE-2-CARBOXAMIDE'>ME5</scene> | |LIGAND= <scene name='pdbligand=ME5:5-CHLORO-N-((1R,2S)-2-(4-(2-OXOPYRIDIN-1(2H)-YL)BENZAMIDO)+CYCLOPENTYL)THIOPHENE-2-CARBOXAMIDE'>ME5</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=[[2p93|2P93]], [[2p94|2P94]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2p95 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2p95 OCA], [http://www.ebi.ac.uk/pdbsum/2p95 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2p95 RCSB]</span> | |||
}} | }} | ||
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==Overview== | ==Overview== | ||
In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties. | In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties. | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Chang, C H.]] | [[Category: Chang, C H.]] | ||
[[Category: blood coagulation factor]] | [[Category: blood coagulation factor]] | ||
[[Category: calcium-binding]] | [[Category: calcium-binding]] | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
''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 04:32:43 2008'' | ||
Revision as of 04:32, 31 March 2008
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| , resolution 2.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Coagulation factor Xa, with EC number 3.4.21.6 | ||||||
| Related: | 2P93, 2P94
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Factor xa in complex with the inhibitor 5-chloro-N-((1R,2S)-2-(4-(2-oxopyridin-1(2H)-YL)benzamido) cyclopentyl)thiophene-2-carboxamide
OverviewOverview
In the search of Factor Xa (FXa) inhibitors structurally different from the pyrazole-based series, we identified a viable series of enantiopure cis-(1R,2S)-cycloalkyldiamine derivatives as potent and selective inhibitors of FXa. Among them, cyclohexyldiamide 7 and cyclopentyldiamide 9 were the most potent neutral compounds, and had good anticoagulant activity comparable to the pyrazole-based analogs. Crystal structures of 7-FXa and 9-FXa illustrate binding similarities and differences between the five- and the six-membered core systems, and provide rationales for the observed SAR of P1 and linker moieties.
About this StructureAbout this Structure
2P95 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
SAR and X-ray structures of enantiopure 1,2-cis-(1R,2S)-cyclopentyldiamine and cyclohexyldiamine derivatives as inhibitors of coagulation Factor Xa., Qiao JX, Chang CH, Cheney DL, Morin PE, Wang GZ, King SR, Wang TC, Rendina AR, Luettgen JM, Knabb RM, Wexler RR, Lam PY, Bioorg Med Chem Lett. 2007 Aug 15;17(16):4419-27. Epub 2007 Jun 10. PMID:17588746
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