Vacuolin-1 | Autophagy/PIKfyve inhibitor

Vacuolin-1 (351986-85-1) inhibits autophagy via inhibition of Ca²⁺-dependent fusion of lysosomes with the plasma membrane and the release of lysosomal content and has no effect on other membrane-bound organelles.¹ It has been shown to block endosome maturation by activating RAB5 which compromises the biogenesis and function of lysosomes including autophagosomal-lysosomal fusion and endosomal-lysosomal degradation.² It potently inhibits migration, invasion and colony formation of cancer cells (which is linked to endosomal trafficking) and targets capping protein Zβ (CapZβ) in these processes.³ Inhibition of lysosomal maturation was shown to be due to potent inhibition of PIKfyve.⁴

References\Citations

1. Cerny et al. (2004), The small chemical vacuolin-1 inhibits Ca(2+)-dependent exocytosis but not cell resealing; EMBO Rep., 5 883
2. Lu et al. (2014), Vacuolin-1 potently and reversibly inhibits autophagosome-lysosome fusion by activating RAB5A; Autophagy, 10 1895
3. Zuodong et al. (2021), Vacuolin-1 inhibits endosomal trafficking and metastasis via CapZß; Oncogene, 40 1775
4. Sano et al. (2016), Vacuolin-1 inhibits autophagy by impairing lysosomal maturation via PIKfyve; FEBS Lett., 590 1576