Recent progress on third generation covalent EGFR inhibitors

被引：86

作者：

Cheng, Hengmiao ^{[1
]}

Nair, Sajiv K. ^{[1
]}

Murray, Brion W. ^{[2
]}

机构：

[1] Pfizer Worldwide Res & Dev, La Jolla Labs, Oncol Med Chem, 10770 Sci Ctr Dr, San Diego, CA 92121 USA

[2] Pfizer Worldwide Res & Dev, La Jolla Labs, Oncol Res Unit, 10770 Sci Ctr Dr, San Diego, CA 92121 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2016年 / 26卷 / 08期

关键词：

EGFR; Covalent inhibitor; T790M; Oncogenic mutation; Lung cancer; NSCLC; SBDD; Drug resistance; CELL LUNG-CANCER; GROWTH-FACTOR RECEPTOR; TYROSINE KINASE INHIBITORS; IRREVERSIBLE INHIBITORS; ACQUIRED-RESISTANCE; DRUG-RESISTANCE; AZD9291; DISCOVERY; MUTATIONS; GEFITINIB;

D O I：

10.1016/j.bmcl.2016.02.067

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

First generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (gefitinib and erlotinib) demonstrate excellent clinical efficacy for NSCLC patients carrying EGFR oncogenic mutations (L858R, del exon 19 deletions between amino acids 746 and 750). Invariable, drug resistance occurs with around 60% of it driven by the EGFR-T790M gatekeeper mutation. To counter the T790M-dependent resistance, third generation covalent EGFR inhibitors have been developed with high potency toward T790M containing mutants and selectivity over WT EGFR. This review provides an overview of the third generation drugs currently in clinical trials and also encompasses novel methodologies developed to discover third generation covalent EGFR drugs. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：1861 / 1868

页数：8

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