9Q319Q31 の概要
| エントリーDOI | 10.2210/pdb9q31/pdb |
| 分子名称 | Receptor-interacting serine/threonine-protein kinase 1, cyclopropyl[(4R,5S,7S)-7-fluoro-5-phenyl-6,7-dihydro-5H-pyrrolo[1,2-b][1,2,4]triazol-2-yl]methanone, BROMIDE ION, ... (7 entities in total) |
| 機能のキーワード | kinase, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor |
| 由来する生物種 | Homo sapiens (human) |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 68445.27 |
| 構造登録者 | |
| 主引用文献 | Patel, S.,Chen, H.,Varfolomeev, E.,Kwon, Y.,Ramaswamy, S.,Kohli, P.B.,Quinn, J.G.,Webster, J.D.,Mao, J.,Chen, Y.,Fong, R.,Demircioglu, F.E.,Lupardus, P.,Stivala, C.,Hamilton, G.L.,Siu, M.,Sujatha-Bhaskar, S.,Mohanan, V.,Adedeji, A.O.,Santagostino, S.F.,Maher, J.,McKenzie, B.,Rothenberg, M.E.,Johnson, A.,Vucic, D. Discovery of Clinical Candidate GDC-8264, a Novel, Potent and Selective RIP1 Inhibitor for Amelioration of Tissue Damage and the Treatment of Inflammatory Diseases. J.Med.Chem., 68:23050-23077, 2025 Cited by PubMed Abstract: Receptor-interacting protein 1 (RIP1) is a critical regulator of inflammatory cell death induced by diverse stimuli including TNF family ligands and ischemic injury. As such, the inhibition of RIP1 with small molecule kinase inhibitors is predicted to ameliorate tissue damage and associated inflammation. A novel ketone class of RIP1 inhibitors was identified via a high-throughput screen followed by structure-based scaffold hopping. Subsequent optimization yielded clinical molecule (compound ), which has excellent target selectivity and druglike attributes for once-daily oral dosing. is currently being tested in a Phase 2 trial for the prevention of cardiac surgery-associated acute kidney injury (CSA-AKI) in hopes of providing benefit for patients requiring cardio-pulmonary bypass at medium to high risk of developing CSA-AKI. PubMed: 41165210DOI: 10.1021/acs.jmedchem.5c01891 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (2.05 Å) |
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