9FQP

EGFR Exon20 insertion mutant NPG bound with Compound 23

これはPDB形式変換不可エントリーです。

9FQP の概要

• エントリーDOI: 10.2210/pdb9fqp/pdb
• 分子名称: Epidermal growth factor receptor, (7~{S})-3-[(3-chloranyl-2-methoxy-phenyl)amino]-2-(3-fluoranylpyridin-4-yl)-7-(2-methoxyethyl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one (3 entities in total)
• 機能のキーワード: kinase, 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: 39122.49

構造登録者

Hilbert, B.J.,Brooijmans, N.,Milgram, B.C.,Pagliarini, R.A. (登録日: 2024-06-17, 公開日: 2025-01-29, 最終更新日: 2025-02-26)

主引用文献

Milgram, B.C.,Borrelli, D.R.,Brooijmans, N.,Henderson, J.A.,Hilbert, B.J.,Huff, M.R.,Ito, T.,Jackson, E.L.,Jonsson, P.,Ladd, B.,O'Hearn, E.L.,Pagliarini, R.A.,Roberts, S.A.,Ronseaux, S.,Stuart, D.D.,Wang, W.,Guzman-Perez, A.
Discovery of STX-721, a Covalent, Potent, and Highly Mutant-Selective EGFR/HER2 Exon20 Insertion Inhibitor for the Treatment of Non-Small Cell Lung Cancer.
J.Med.Chem., 68:2403-2421, 2025

PubMed Abstract: After L858R and ex19del epidermal growth factor receptor (EGFR) mutations, ex20ins mutations are the third most common class of driver-mutations in non-small cell lung cancer (NSCLC). Unfortunately, first-, second-, and third-generation EGFR tyrosine kinase inhibitors (TKIs) are generally ineffective for ex20ins patients due to insufficient mutant activity and selectivity over wild-type EGFR, leading to dose-limiting toxicities. While significant advances in recent years have been made toward identifying potent EGFR ex20ins mutant inhibitors, mutant vs wild-type EGFR selectivity remains a significant challenge. STX-721 () is a potent, irreversible inhibitor of the majority of EGFR/HER2 ex20ins mutants and demonstrates excellent mutant vs wild-type selectivity both in vitro and in vivo. STX-721 is currently in phase 1/2 clinical trials for EGFR/HER2 ex20ins-driven NSCLC.

PubMed: 39824516
DOI: 10.1021/acs.jmedchem.4c02377

実験手法

X-RAY DIFFRACTION (2.495 Å)