AR7

AR7 (CAS No.: 80306-38-3) is a small-molecule atypical antagonist of retinoic acid receptor alpha (RARα) that functions as a selective activator of chaperone-mediated autophagy (CMA), positioning it as a valuable chemical probe for studying lysosome-dependent protein quality control pathways. Mechanistically, AR7 enhances CMA activity in an RARα-dependent manner, associated with upregulation of key lysosomal components such as LAMP-2A, while notably sparing macroautophagy, thereby enabling selective interrogation of CMA-specific processes without broadly perturbing autophagic flux. In cellular systems, AR7 has been shown to increase lysosomal activity in both wild-type and mutant models, including LRRK2 R1441G knock-in fibroblasts, and to protect against stress-induced cytotoxicity, such as paraquat-mediated cell damage, consistent with enhanced proteostatic capacity. Its activity is typically observed in the low to moderate micromolar range in vitro, and it exhibits context-dependent cytotoxicity, including preferential effects under hypoxic conditions in certain cancer cell lines. AR7 is widely applied in studies of neurodegeneration, particularly Parkinson’s disease models characterized by impaired protein degradation, as well as in investigations of aging, proteostasis, and lysosomal function. Experimental usage concentrations and treatment durations vary depending on cell type and assay design, but it is commonly employed in micromolar ranges for mechanistic and phenotypic studies in both cellular and preclinical research settings.