9DF2

EGFR Exon20 insertion mutant ASV bound with (S)-3-((3-chloro-2-methoxyphenyl)amino)-2-(3-((tetrahydrofuran-2-yl)methoxy)pyridin-4-yl)-1,5,6,7-tetrahydro-4H-pyrrolo[3,2-c]pyridin-4-one

これはPDB形式変換不可エントリーです。

9DF2 の概要

• エントリーDOI: 10.2210/pdb9df2/pdb
• 分子名称: Epidermal growth factor receptor, 3-[(3-chloranyl-2-methoxy-phenyl)amino]-2-[3-[[(2S)-oxolan-2-yl]methoxy]pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one, CHLORIDE ION, ... (7 entities in total)
• 機能のキーワード: kinase, inhibitor, oncoprotein, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 39171.95

構造登録者

Hilbert, B.J. (登録日: 2024-08-29, 公開日: 2025-05-14, 最終更新日: 2025-07-23)

主引用文献

Pagliarini, R.A.,Henderson, J.A.,Milgram, B.C.,Borrelli, D.R.,Brooijmans, N.,Hilbert, B.J.,Huff, M.R.,Ito, T.,Kryukov, G.V.,Ladd, B.,Martin, B.R.,Motiwala, H.,O'Hearn, E.,Tsai, C.F.,Wang, W.,Bellier, J.,Boland, L.,Clark, S.,Hensley, E.,Hata, A.N.,Kuzmic, P.,Guzman-Perez, A.,Jackson, E.L.,Stuart, D.D.
STX-721, a Covalent EGFR/HER2 Exon 20 Inhibitor, Utilizes Exon 20-Mutant Dynamic Protein States and Achieves Unique Mutant Selectivity Across Human Cancer Models.
Clin.Cancer Res., 31:3002-3018, 2025

PubMed Abstract: Commonly occurring oncogenic mutations in EGFR render non-small cell lung cancers sensitive to approved EGFR-targeted drugs. EGFR in-frame exon 20 insertion (ex20ins) mutants are, however, less sensitive to such drugs. The efficacy of existing medicines may in part be limited by their selectivity for ex20ins mutations relative to wild-type EGFR, which is important for epithelial tissue homeostasis.

PubMed: 40465424
DOI: 10.1158/1078-0432.CCR-24-3833

実験手法

X-RAY DIFFRACTION (2.5 Å)