Autophinib

Autophinib (CAS No.: 1644443-47-9) is a potent and selective small-molecule inhibitor of autophagy that functions primarily through ATP-competitive inhibition of the class III phosphatidylinositol 3-kinase VPS34, a key regulator of autophagosome formation and vesicular trafficking. By targeting VPS34, Autophinib effectively suppresses autophagy induced by nutrient deprivation or mTOR inhibition, demonstrating strong activity in cell-based systems with inhibitory effects observed in the nanomolar range for both starvation- and rapamycin-induced autophagic processes. Mechanistically, it reduces LC3 lipidation and the formation of LC3-II while preventing degradation of the autophagy substrate p62, consistent with blockade of autophagic flux. In cancer cell models such as MCF-7, Autophinib has also been shown to promote apoptosis under nutrient-starved conditions, indicating a functional link between autophagy inhibition and cell survival pathways. As a research tool, it is widely applied in studies investigating autophagy regulation, VPS34 signaling, and the interplay between autophagy and apoptosis, as well as in drug discovery efforts targeting autophagy-dependent diseases; experimental concentrations typically vary depending on assay design and biological context.