MET has been considered as a promising drug target for the treatment of MET-dependent diseases, particularly non-small cell lung cancer (NSCLC). Small molecule MET inhibitors with mainly three types of binding 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 development and discovery strategies utilized for MET inhibitors as well as mechanisms of acquired resistance to current approved inhibitors. The insights will accelerate discovery of new generation MET inhibitors to overcome clinical acquired resistance.
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机译:MET被认为是治疗MET依赖性疾病,特别是非小细胞肺癌(NSCLC)的有前途的药物靶点。已经开发出主要具有三种结合模式(Ia/Ib、II 和 III)的小分子 MET 抑制剂。本文综述了MET的结构特征、激活机制和失调途径,并总结了MET抑制剂的开发和发现策略的进展,以及对目前已获批抑制剂的获得性耐药机制。这些见解将加速新一代MET抑制剂的发现,以克服临床获得性耐药性。
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