7ER2

Crystal structure of EGFR 696-1022 T790M/C797S in complex with LS_2_40

7ER2 の概要

• エントリーDOI: 10.2210/pdb7er2/pdb
• 分子名称: Epidermal growth factor receptor, 5-chloranyl-N2-[3-chloranyl-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-N4-(2-dimethylphosphorylphenyl)pyrimidine-2,4-diamine (3 entities in total)
• 機能のキーワード: egfr, t790m/c797s, 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: 38048.88

構造登録者

Zhu, S.J.,Yun, C.H. (登録日: 2021-05-05, 公開日: 2022-04-20, 最終更新日: 2023-11-29)

主引用文献

Li, S.,Zhang, T.,Zhu, S.J.,Lei, C.,Lai, M.,Peng, L.,Tong, L.,Pang, Z.,Lu, X.,Ding, J.,Ren, X.,Yun, C.H.,Xie, H.,Ding, K.
Optimization of Brigatinib as New Wild-Type Sparing Inhibitors of EGFR T790M/C797S Mutants.
Acs Med.Chem.Lett., 13:196-202, 2022

PubMed Abstract: A series of brigatinib derivatives were designed and synthesized as new potent and selective EGFR inhibitors. One of the most potent and selective compounds strongly suppressed the EGFR and EGFR kinases with IC values of 0.7 and 3.6 nM, respectively, which were over 54-fold more potent than the lead compound. also demonstrated promising EGFR mutant selectivity, and was 94-fold less potent against the wild type EGFR. A cocrystal structure of EGFR with a close derivative was solved to provide insight on the inhibitor's binding mode. Moreover, compound was orally bioavailable and demonstrated highly desirable PK properties, making it a promising lead compound for further structural optimization.

PubMed: 35178175
DOI: 10.1021/acsmedchemlett.1c00555

実験手法

X-RAY DIFFRACTION (2.662 Å)