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

2ICA の概要

• エントリーDOI: 10.2210/pdb2ica/pdb
• 分子名称: 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)
• 機能のキーワード: inhibitor, protein-ligand complex, cell adhesion
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Cell membrane ; Single-pass type I membrane protein : P20701
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 21491.41

構造登録者

Sheriff, S.,Einspahr, H. (登録日: 2006-09-12, 公開日: 2006-12-19, 最終更新日: 2023-08-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (1.56 Å)