6OKO

Crystal structure of mRIPK3 complexed with N-(3-fluoro-4-{1H-pyrrolo[2,3-b]pyridin-4-yloxy}phenyl)-1-(4-fluorophenyl)-2-oxo-1,2-dihydropyridine-3-carboxamide

6OKO の概要

• エントリーDOI: 10.2210/pdb6oko/pdb
• 分子名称: Receptor-interacting serine/threonine-protein kinase 3, 1-(4-fluorophenyl)-N-[3-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)phenyl]-2-oxo-1,2-dihydropyridine-3-carboxamide (3 entities in total)
• 機能のキーワード: kinase, ripk3, rip3, transferase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 73343.49

構造登録者

Pokross, M.E. (登録日: 2019-04-14, 公開日: 2019-07-17, 最終更新日: 2024-03-13)

主引用文献

Hart, A.C.,Abell, L.,Guo, J.,Mertzman, M.E.,Padmanabha, R.,Macor, J.E.,Chaudhry, C.,Lu, H.,O'Malley, K.,Shaw, P.J.,Weigelt, C.,Pokross, M.,Kish, K.,Kim, K.S.,Cornelius, L.,Douglas, A.E.,Calambur, D.,Zhang, P.,Carpenter, B.,Pitts, W.J.
Identification of RIPK3 Type II Inhibitors Using High-Throughput Mechanistic Studies in Hit Triage.
Acs Med.Chem.Lett., 11:266-271, 2020

PubMed Abstract: Necroptosis has been implicated in a variety of disease states, and RIPK3 is one of the kinases identified to play a critical role in this signaling pathway. In an effort to identify RIPK3 kinase inhibitors with a novel profile, mechanistic studies were incorporated at the hit triage stage. Utilization of these assays enabled identification of a Type II DFG-out inhibitor for RIPK3, which was confirmed by protein crystallography. Structure-based drug design on the inhibitors targeting this previously unreported conformation enabled an enhancement in selectivity against key off-target kinases.

PubMed: 32184955
DOI: 10.1021/acsmedchemlett.9b00065

実験手法

X-RAY DIFFRACTION (2.1 Å)