Unraveling the Roles of Protein Kinases in Autophagy: An Update on Small-Molecule Compounds for Targeted Therapy.

Protein kinases, which catalyze the phosphorylation of proteins, are involved in several important cellular processes, such as autophagy. Of note, autophagy, originally described as a mechanism for intracellular waste disposal and recovery, has been becoming a crucial biological process closely related to many types of human diseases. More recently, the roles of protein kinases in autophagy have been gradually elucidated, and the design of small-molecule compounds to modulate targets to positively or negatively interfere with the cytoprotective autophagy or autophagy-associated cell death may provide a new clue on the current targeted therapy. Thus, in this Perspective, we focus on summarizing the different roles of protein kinases, including positive, negative, and bidirectional regulations of autophagy. Moreover, we discuss several small-molecule compounds targeting these protein kinases in human diseases, highlighting their pivotal roles in autophagy for targeted therapeutic purposes.