Targeting MET: Discovery of Small Molecule Inhibitors as Non-Small Cell Lung Cancer Therapy
Chaofan Wang, Xiaoyun Lu
Abstract
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.
Topics & Concepts
Small moleculeDrug discoveryChemistryMechanism (biology)CancerLung cancerCancer researchPharmacologyComputational biologyMedicineOncologyInternal medicineBiochemistryBiologyPhilosophyEpistemologyLiver physiology and pathologyEnzyme function and inhibitionCancer Mechanisms and Therapy