期刊
JOURNAL OF MEDICINAL CHEMISTRY
卷 -, 期 -, 页码 -出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.3c00028
关键词
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MET is a promising drug target for the treatment of MET-dependent diseases, especially NSCLC. Small molecule MET inhibitors with three types of binding modes have been developed. This review provides an overview of MET's structural features, activation mechanism, dysregulation pathway, and the development strategies of MET inhibitors, as well as the acquired resistance mechanisms. These insights will accelerate the discovery of new generation MET inhibitors to overcome clinical acquired resistance.
MET has been considered as a promising drug target forthe treatmentof MET-dependent diseases, particularly non-small cell lung cancer(NSCLC). Small molecule MET inhibitors with mainly three types ofbinding modes (Ia/Ib, II, and III) have been developed. In this Review,we provide an overview of the structural features, activation mechanism,and dysregulation pathway of MET and summarize progress on the developmentand discovery strategies utilized for MET inhibitors as well as mechanismsof acquired resistance to current approved inhibitors. The insightswill accelerate discovery of new generation MET inhibitors to overcomeclinical acquired resistance.
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