Recent updates on third generation EGFR inhibitors and emergence of fourth generation EGFR inhibitors to combat C797S resistance

被引：127

作者：

Patel, Harun ^{[1
]}

Pawara, Rahul ^{[1
]}

Ansari, Azim ^{[1
]}

Surana, Sanjay ^{[1
]}

机构：

[1] RC Patel Inst Pharmaceut Educ & Res, Dept Pharmaceut Chem, Div Comp Aided Drug Design, Shirpur 425405, Maharashtra, India

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2017年 / 142卷

关键词：

Non-small cell lung cancer; T790M EGFR; C7975; EGFR; Fourth generation EGFR inhibitors; CELL LUNG-CANCER; TYROSINE KINASE INHIBITORS; ACQUIRED-RESISTANCE; T790M-MEDIATED RESISTANCE; T790M-POSITIVE NSCLC; NEXT-GENERATION; AZD9291; MUTATIONS; CHEMOTHERAPY; GEFITINIB;

D O I：

10.1016/j.ejmech.2017.05.027

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

EGFR T790M mutation leads to resistance to most of clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development, which includes osimertinib, rociletinib, HM61713, ASP8273, EGF816, and PF-06747775. On the other hand recently EGFR C797S mutation was reported to be a leading mechanism of resistance to the third-generation inhibitors. The C797S mutation appears to be an ideal target for overcoming the acquired resistance to the third generation inhibitors. This review summarizes the third generation inhibitors, synthesis, their mechanism of resistance and latest development on the discovery of a fourth-generation EGFR This and U to Y allosteric strategies to combat the C797S EGFR resistance problem. (C) 2017 Elsevier Masson SAS. All rights reserved.

引用

页码：32 / 47

页数：16

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