7B44

Crystal structure of c-MET bound by compound S1

7B44 の概要

• エントリーDOI: 10.2210/pdb7b44/pdb
• 分子名称: Hepatocyte growth factor receptor, 5-methoxy-1~{H}-indazole, DIMETHYL SULFOXIDE, ... (5 entities in total)
• 機能のキーワード: c-met, kinase, folded p-loop, inhibitor, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 34474.89

構造登録者

Collie, G.W. (登録日: 2020-12-02, 公開日: 2020-12-09, 最終更新日: 2024-05-01)

主引用文献

Collie, G.W.,Michaelides, I.N.,Embrey, K.,Stubbs, C.J.,Borjesson, U.,Dale, I.L.,Snijder, A.,Barlind, L.,Song, K.,Khurana, P.,Phillips, C.,Storer, R.I.
Structural Basis for Targeting the Folded P-Loop Conformation of c-MET.
Acs Med.Chem.Lett., 12:162-167, 2021

PubMed Abstract: We report here a fragment screen directed toward the c-MET kinase from which we discovered a series of inhibitors able to bind to a rare conformation of the protein in which the P-loop adopts a collapsed, or folded, arrangement. Preliminary SAR exploration led to an inhibitor () with nanomolar biochemical activity against c-MET and promising cell activity and kinase selectivity. These findings increase our structural understanding of the folded P-loop conformation of c-MET and provide a sound structural and chemical basis for further investigation of this underexplored yet potentially therapeutically exploitable conformational state.

PubMed: 33488978
DOI: 10.1021/acsmedchemlett.0c00392

実験手法

X-RAY DIFFRACTION (1.76 Å)