5J9Z

EGFR-T790M in complex with pyrazolopyrimidine inhibitor 1a

5J9Z の概要

• エントリーDOI: 10.2210/pdb5j9z/pdb
• 分子名称: Epidermal growth factor receptor, (R)-1-(3-(4-amino-3-(1-methyl-1H-indol-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidin-1-yl)prop-2-en-1-one (3 entities in total)
• 機能のキーワード: tyrosine kinase, covalent inhibitor, drug resistance, 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: 37550.50

構造登録者

Becker, C.,Engel, J.,Rauh, D. (登録日: 2016-04-11, 公開日: 2016-08-17, 最終更新日: 2024-10-23)

主引用文献

Engel, J.,Becker, C.,Lategahn, J.,Keul, M.,Ketzer, J.,Muhlenberg, T.,Kollipara, L.,Schultz-Fademrecht, C.,Zahedi, R.P.,Bauer, S.,Rauh, D.
Insight into the Inhibition of Drug-Resistant Mutants of the Receptor Tyrosine Kinase EGFR.
Angew.Chem.Int.Ed.Engl., 55:10909-10912, 2016

PubMed Abstract: Targeting acquired drug resistance represents the major challenge in the treatment of EGFR-driven non-small-cell lung cancer (NSCLC). Herein, we describe the structure-based design, synthesis, and biological evaluation of a novel class of covalent EGFR inhibitors that exhibit excellent inhibition of EGFR-mutant drug-resistant cells. Protein X-ray crystallography combined with detailed kinetic studies led to a deeper understanding of the mode of inhibition of EGFR-T790M and provided insight into the key principles for effective inhibition of the recently discovered tertiary mutation at EGFR-C797S.

PubMed: 27496389
DOI: 10.1002/anie.201605011

実験手法

X-RAY DIFFRACTION (2.5 Å)