5EYC

Crystal structure of c-Met in complex with naphthyridinone inhibitor 5

5EYC の概要

• エントリーDOI: 10.2210/pdb5eyc/pdb
• 関連するPDBエントリー: 5EYD
• 分子名称: Hepatocyte growth factor receptor, 6-[(1~{R})-1-[8-fluoranyl-6-(3-methyl-1,2-oxazol-5-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl]ethyl]-1,6-naphthyridin-5-one (3 entities in total)
• 機能のキーワード: phosphotransferase, inhibitor, cancer, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Membrane; Single-pass type I membrane protein. Isoform 3: Secreted: P08581
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 35606.09

構造登録者

Whittington, D.A.,Long, A.M. (登録日: 2015-11-24, 公開日: 2016-02-10, 最終更新日: 2023-09-27)

主引用文献

Boezio, A.A.,Copeland, K.W.,Rex, K.,K Albrecht, B.,Bauer, D.,Bellon, S.F.,Boezio, C.,Broome, M.A.,Choquette, D.,Coxon, A.,Dussault, I.,Hirai, S.,Lewis, R.,Lin, M.H.,Lohman, J.,Liu, J.,Peterson, E.A.,Potashman, M.,Shimanovich, R.,Teffera, Y.,Whittington, D.A.,Vaida, K.R.,Harmange, J.C.
Discovery of (R)-6-(1-(8-Fluoro-6-(1-methyl-1H-pyrazol-4-yl)-[1,2,4]triazolo[4,3-a]pyridin-3-yl)ethyl)-3-(2-methoxyethoxy)-1,6-naphthyridin-5(6H)-one (AMG 337), a Potent and Selective Inhibitor of MET with High Unbound Target Coverage and Robust In Vivo Antitumor Activity.
J.Med.Chem., 59:2328-2342, 2016

PubMed Abstract: Deregulation of the receptor tyrosine kinase mesenchymal epithelial transition factor (MET) has been implicated in several human cancers and is an attractive target for small molecule drug discovery. Herein, we report the discovery of compound 23 (AMG 337), which demonstrates nanomolar inhibition of MET kinase activity, desirable preclinical pharmacokinetics, significant inhibition of MET phosphorylation in mice, and robust tumor growth inhibition in a MET-dependent mouse efficacy model.

PubMed: 26812066
DOI: 10.1021/acs.jmedchem.5b01716

実験手法

X-RAY DIFFRACTION (1.8 Å)