2ica
From Proteopedia
| Line 1: | Line 1: | ||
| - | [[Image:2ica.gif|left|200px]] | + | [[Image:2ica.gif|left|200px]] |
| - | + | ||
| - | '''CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro [4.4]non-7-yl]methyl]-3-thiophenecarboxylicacid''' | + | {{Structure |
| + | |PDB= 2ica |SIZE=350|CAPTION= <scene name='initialview01'>2ica</scene>, resolution 1.56Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=2IC:5-[(5S,9R)-9-(4-CYANOPHENYL)-3-(3,5-DICHLOROPHENYL)-1-METHYL-2,4-DIOXO-1,3,7-TRIAZASPIRO [4.4]NON-7-YL]METHYL]-3-THIOPHENECARBOXYLICACID'>2IC</scene> | ||
| + | |ACTIVITY= | ||
| + | |GENE= ITGAL, CD11A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 Homo sapiens]) | ||
| + | }} | ||
| + | |||
| + | '''CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro [4.4]non-7-yl]methyl]-3-thiophenecarboxylicacid''' | ||
| + | |||
==Overview== | ==Overview== | ||
| Line 7: | Line 16: | ||
==About this Structure== | ==About this Structure== | ||
| - | 2ICA is a [ | + | 2ICA is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ICA OCA]. |
==Reference== | ==Reference== | ||
| - | Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3 ,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1., Potin D, Launay M, Monatlik F, Malabre P, Fabreguettes M, Fouquet A, Maillet M, Nicolai E, Dorgeret L, Chevallier F, Besse D, Dufort M, Caussade F, Ahmad SZ, Stetsko DK, Skala S, Davis PM, Balimane P, Patel K, Yang Z, Marathe P, Postelneck J, Townsend RM, Goldfarb V, Sheriff S, Einspahr H, Kish K, Malley MF, DiMarco JD, Gougoutas JZ, Kadiyala P, Cheney DL, Tejwani RW, Murphy DK, Mcintyre KW, Yang X, Chao S, Leith L, Xiao Z, Mathur A, Chen BC, Wu DR, Traeger SC, McKinnon M, Barrish JC, Robl JA, Iwanowicz EJ, Suchard SJ, Dhar TG, J Med Chem. 2006 Nov 30;49(24):6946-9. PMID:[http:// | + | Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3 ,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1., Potin D, Launay M, Monatlik F, Malabre P, Fabreguettes M, Fouquet A, Maillet M, Nicolai E, Dorgeret L, Chevallier F, Besse D, Dufort M, Caussade F, Ahmad SZ, Stetsko DK, Skala S, Davis PM, Balimane P, Patel K, Yang Z, Marathe P, Postelneck J, Townsend RM, Goldfarb V, Sheriff S, Einspahr H, Kish K, Malley MF, DiMarco JD, Gougoutas JZ, Kadiyala P, Cheney DL, Tejwani RW, Murphy DK, Mcintyre KW, Yang X, Chao S, Leith L, Xiao Z, Mathur A, Chen BC, Wu DR, Traeger SC, McKinnon M, Barrish JC, Robl JA, Iwanowicz EJ, Suchard SJ, Dhar TG, J Med Chem. 2006 Nov 30;49(24):6946-9. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17125246 17125246] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
| Line 19: | Line 28: | ||
[[Category: protein/ligand complex]] | [[Category: protein/ligand complex]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:27:49 2008'' |
Revision as of 15:27, 20 March 2008
| |||||||
| , resolution 1.56Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Gene: | ITGAL, CD11A (Homo sapiens) | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CD11a (LFA1) I-domain complexed with BMS-587101 aka 5-[(5S, 9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro [4.4]non-7-yl]methyl]-3-thiophenecarboxylicacid
Overview
LFA-1 (leukocyte function-associated antigen-1), is a member of the beta2-integrin family and is expressed on all leukocytes. This letter describes the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1 antagonists that culminated in the identification of analog 8 as a clinical candidate. We also report the first example of the efficacy of a small molecule LFA-1 antagonist in combination with CTLA-4Ig in an animal model of transplant rejection.
About this Structure
2ICA is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3 ,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1., Potin D, Launay M, Monatlik F, Malabre P, Fabreguettes M, Fouquet A, Maillet M, Nicolai E, Dorgeret L, Chevallier F, Besse D, Dufort M, Caussade F, Ahmad SZ, Stetsko DK, Skala S, Davis PM, Balimane P, Patel K, Yang Z, Marathe P, Postelneck J, Townsend RM, Goldfarb V, Sheriff S, Einspahr H, Kish K, Malley MF, DiMarco JD, Gougoutas JZ, Kadiyala P, Cheney DL, Tejwani RW, Murphy DK, Mcintyre KW, Yang X, Chao S, Leith L, Xiao Z, Mathur A, Chen BC, Wu DR, Traeger SC, McKinnon M, Barrish JC, Robl JA, Iwanowicz EJ, Suchard SJ, Dhar TG, J Med Chem. 2006 Nov 30;49(24):6946-9. PMID:17125246
Page seeded by OCA on Thu Mar 20 17:27:49 2008
