Abstract
Autophagy is an essential homeostatic and catabolic process crucial for the degradation or recycling of proteins and cellular components. Drug resistance has been demonstrated to be closely implicated in increased autophagy. Autophagy inhibition to reverse drug resistance involves in the five stages of autophagy, including phagophore initiation, vesicle nucleation, vesicle elongation, vesicle fusion and cargo degradation. Herein, emphases were placed on discussions on the targets responsible for the upstream phagophore initiation and nucleation of autophagosome, as well as the ones mediating the downstream autophagosome and lysosome fusion and cargo degradation. The structure-activity relationships (SARs) and action mechanisms of the corresponding target-based small molecule autophagy inhibitors were analyzed and delineated. This review will provide a promising guidance for the design and optimization of drug-like scaffolds in the discovery of autophagy inhibitors able to eliminate drug resistance.
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