2ICA

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

Summary for 2ICA

• Entry DOI: 10.2210/pdb2ica/pdb
• Descriptor: Integrin alpha-L, 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 (3 entities in total)
• Functional Keywords: inhibitor, protein-ligand complex, cell adhesion
• Biological source: Homo sapiens (human)
• Cellular location: Cell membrane ; Single-pass type I membrane protein : P20701
• Total number of polymer chains: 1
• Total formula weight: 21491.41

Authors

Sheriff, S.,Einspahr, H. (deposition date: 2006-09-12, release date: 2006-12-19, Last modification date: 2023-08-30)

Primary citation

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, S.Z.,Stetsko, D.K.,Skala, S.,Davis, P.M.,Balimane, P.,Patel, K.,Yang, Z.,Marathe, P.,Postelneck, J.,Townsend, R.M.,Goldfarb, V.,Sheriff, S.,Einspahr, H.,Kish, K.,Malley, M.F.,Dimarco, J.D.,Gougoutas, J.Z.,Kadiyala, P.,Cheney, D.L.,Tejwani, R.W.,Murphy, D.K.,McIntyre, K.W.,Yang, X.,Chao, S.,Leith, L.,Xiao, Z.,Mathur, A.,Chen, B.C.,Wu, D.R.,Traeger, S.C.,McKinnon, M.,Barrish, J.C.,Robl, J.A.,Iwanowicz, E.J.,Suchard, S.J.,Dhar, T.G.
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 Leukocyte Function Associated Antigen-1.
J.Med.Chem., 49:6946-6949, 2006

PubMed Abstract: 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.

PubMed: 17125246
DOI: 10.1021/jm0610806

Experimental method

X-RAY DIFFRACTION (1.56 Å)