Discovery of selective irreversible inhibitors for EGFR-T790M

被引：56

作者：

Zhou, Wenjun ^{[1
,2
]}

Ercan, Dalia ^{[3
,4
]}

Jaenne, Pasi A. ^{[3
,4
,5
]}

Gray, Nathanael S. ^{[1
,2
]}

机构：

[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA

[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA

[3] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[5] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 02期

关键词：

EGFR; Kinase inhibitor; T790M; Mutant selective; ACQUIRED-RESISTANCE; KINASE INHIBITORS; EGFR; RECEPTOR; CANCER;

D O I：

10.1016/j.bmcl.2010.12.036

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.

引用

页码：638 / 643

页数：6

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