5J7B

The identification and pharmacological characterization of 6-(tert-butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a highly potent and selective inhibitor of RIP2 Kinase, GSK583 complex

5J7B の概要

• エントリーDOI: 10.2210/pdb5j7b/pdb
• 関連するPDBエントリー: 5J79
• 分子名称: Receptor-interacting serine/threonine-protein kinase 2, 6-(tert-butylsulfonyl)-N-(5-fluoro-2H-indazol-3-yl)quinolin-4-amine (3 entities in total)
• 機能のキーワード: kinase domain, kinase inhibitor, structure-based drug design, inhibitor selectivity, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm : O43353
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 76008.87

構造登録者

Convery, M.A.,Casillas, L.N.,Haile, P.A.,Votta, B.J.,Lakdawala, A.S. (登録日: 2016-04-06, 公開日: 2016-05-18, 最終更新日: 2023-09-27)

主引用文献

Haile, P.A.,Votta, B.J.,Marquis, R.W.,Bury, M.J.,Mehlmann, J.F.,Singhaus, R.,Charnley, A.K.,Lakdawala, A.S.,Convery, M.A.,Lipshutz, D.B.,Desai, B.M.,Swift, B.,Capriotti, C.A.,Berger, S.B.,Mahajan, M.K.,Reilly, M.A.,Rivera, E.J.,Sun, H.H.,Nagilla, R.,Beal, A.M.,Finger, J.N.,Cook, M.N.,King, B.W.,Ouellette, M.T.,Totoritis, R.D.,Pierdomenico, M.,Negroni, A.,Stronati, L.,Cucchiara, S.,Ziokowski, B.,Vossenkamper, A.,MacDonald, T.T.,Gough, P.J.,Bertin, J.,Casillas, L.N.
The Identification and Pharmacological Characterization of 6-(tert-Butylsulfonyl)-N-(5-fluoro-1H-indazol-3-yl)quinolin-4-amine (GSK583), a Highly Potent and Selective Inhibitor of RIP2 Kinase.
J.Med.Chem., 59:4867-4880, 2016

PubMed Abstract: RIP2 kinase is a central component of the innate immune system and enables downstream signaling following activation of the pattern recognition receptors NOD1 and NOD2, leading to the production of inflammatory cytokines. Recently, several inhibitors of RIP2 kinase have been disclosed that have contributed to the fundamental understanding of the role of RIP2 in this pathway. However, because they lack either broad kinase selectivity or strong affinity for RIP2, these tools have only limited utility to assess the role of RIP2 in complex environments. We present, herein, the discovery and pharmacological characterization of GSK583, a next-generation RIP2 inhibitor possessing exquisite selectivity and potency. Having demonstrated the pharmacological precision of this tool compound, we report its use in elucidating the role of RIP2 kinase in a variety of in vitro, in vivo, and ex vivo experiments, further clarifying our understanding of the role of RIP2 in NOD1 and NOD2 mediated disease pathogenesis.

PubMed: 27109867
DOI: 10.1021/acs.jmedchem.6b00211

実験手法

X-RAY DIFFRACTION (2.53 Å)