7OXB

Crystal structure of EGFR double mutant (T790M/L858R) in complex with compound 6.

7OXB の概要

• エントリーDOI: 10.2210/pdb7oxb/pdb
• 分子名称: Epidermal growth factor receptor, 2-[2-(3-methoxyphenyl)pyrimidin-4-yl]-1'-prop-2-enoyl-spiro[5,6-dihydro-1~{H}-pyrrolo[3,2-c]pyridine-7,4'-piperidine]-4-one (3 entities in total)
• 機能のキーワード: kinase, inhibitor, egfr, mutant, 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: 37767.77

構造登録者

Collie, G.W. (登録日: 2021-06-22, 公開日: 2021-10-20, 最終更新日: 2024-11-13)

主引用文献

Hoogenboom, N.,Demont, D.,de Zwart, E.,Verkaik, S.,Emmelot, M.,van de Kar, B.,Kaptein, A.,Barf, T.
Discovery and optimization of covalent EGFR T790M/L858R mutant inhibitors".
Bioorg.Med.Chem.Lett., :128406-128406, 2021

PubMed Abstract: Epidermal growth factor receptor (EGFR) inhibitors have clinical utility in the treatment of non-small cell lung cancer (NSCLC) patients. Despite encouraging clinical efficacy with these agents, many patients develop resistance due to sensitizing (or activating) mutations ultimately leading to disease progression. In the majority of the cases, this resistance is due to the T790M mutation and frequently coexisting L858R. In addition, EGFR wild type receptor inhibition can lead to on target related dose limiting toxicities such as rash and diarrhea. We describe herein the identification of a mutant selective lead compound 12, an irreversible covalent inhibitor of EGFR T790M/L858R resistance mutations with selectivity over the wild type form. Significant tumor growth inhibition in preclinical models was observed with this lead.

PubMed: 34624491
DOI: 10.1016/j.bmcl.2021.128406

実験手法

X-RAY DIFFRACTION (2.56 Å)