8ANS

Crystal structure of D1228V c-MET bound by compound 1.

8ANS の概要

• エントリーDOI: 10.2210/pdb8ans/pdb
• 分子名称: Hepatocyte growth factor receptor, GLYCEROL, 3-[bis(fluoranyl)methyl]-~{N}-methyl-~{N}-[(1~{R})-8-methyl-5-(3-methyl-1~{H}-indazol-6-yl)-1,2,3,4-tetrahydronaphthalen-1-yl]pyridine-2-carboxamide, ... (4 entities in total)
• 機能のキーワード: kinase, inhibitor, ac-helix, cancer, 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: 34008.52

構造登録者

Collie, G.W. (登録日: 2022-08-05, 公開日: 2022-08-31, 最終更新日: 2024-01-31)

主引用文献

Collie, G.W.,Barlind, L.,Bazzaz, S.,Borjesson, U.,Dale, I.L.,Disch, J.S.,Habeshian, S.,Jetson, R.,Khurana, P.,Madin, A.,Michaelides, I.N.,Peng, L.,Snijder, A.,Stubbs, C.J.
Discovery of a selective c-MET inhibitor with a novel binding mode.
Bioorg.Med.Chem.Lett., 75:128948-128948, 2022

PubMed Abstract: The c-MET receptor tyrosine kinase has received considerable attention as a cancer drug target yet there remains a need for inhibitors which are selective for c-MET and able to target emerging drug-resistant mutants. We report here the discovery, by screening a DNA-encoded chemical library, of a highly selective c-MET inhibitor which was shown by X-ray crystallography to bind to the kinase in an unprecedented manner. These results represent a novel mode of inhibiting c-MET with a small molecule and may provide a route to targeting drug-resistant forms of the kinase whilst avoiding potential toxicity issues associated with broad kinome inhibition.

PubMed: 35987508
DOI: 10.1016/j.bmcl.2022.128948

実験手法

X-RAY DIFFRACTION (2.01 Å)