2ica
From Proteopedia
(New page: 200px<br /> <applet load="2ica" size="450" color="white" frame="true" align="right" spinBox="true" caption="2ica, resolution 1.56Å" /> '''CD11a (LFA1) I-doma...) |
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| - | [[Image:2ica.gif|left|200px]]<br /> | + | [[Image:2ica.gif|left|200px]]<br /><applet load="2ica" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="2ica" size=" | + | |
caption="2ica, resolution 1.56Å" /> | caption="2ica, resolution 1.56Å" /> | ||
'''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'''<br /> | '''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'''<br /> | ||
==Overview== | ==Overview== | ||
| - | LFA-1 (leukocyte function-associated antigen-1), is a member of the | + | 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== | ==About this Structure== | ||
| - | 2ICA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with 2IC as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 2ICA is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=2IC:'>2IC</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ICA OCA]. |
==Reference== | ==Reference== | ||
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[[Category: protein/ligand complex]] | [[Category: protein/ligand complex]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 17:51:11 2008'' |
Revision as of 15:51, 21 February 2008
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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 with as ligand. 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 Feb 21 17:51:11 2008
