Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve inhibition

Lysosomal protein degradation via Autophagy strictly regulates cellular protein homoeostasis. Herein we performed high-content screening to identify compounds that inhibit Autophagy pathways. We obtained 11 hit compounds and performed cluster analysis using cellular morphological information. Vacuolin-1, which induces the formation of giant vacuoles and is a target unknown compound, clustered with the known PIKfyve Inhibitor YM201636. We further confirmed that vacuolin-1 is a potent PIKfyve Inhibitor, and we finally concluded that PIKfyve inhibitors are novel chemical tools for regulating Autophagy.