A VPS34 inhibitor
Autophinib is a potent, selective autophagy inhibitor with IC50s of 90 nM and 40 nM for starvation- and Rapamycin-induced autophagy, respectively. Autophinib is also an ATP competitive Vacuolar Protein Sorting 34 (VPS34) inhibitor with an IC50 of 19 nM. Autophinib inhibits autophagy induced by starvation or Rapamycin by targeting VPS34[1].
Autophinib (0.01-1 μM) inhibits LC3 lipidation to form LC3-II in a dose-dependent manner in starved MCF7-LC3 cells. Consistent with inhibition of autophagic flux, Autophinib also inhibits p62 degradation by autophagy dose-dependently in MCF7-LC3 cells[1].Autophinib enhances cell death (EC50 of 264 nM) of starved cells as compared to fed cells, which occurred via the induction of apoptosis (EC50 of 234 nM) in MCF7 cells[1].
参考文献:
[1]. Robke L, et al. Phenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34. Angew Chem Int Ed Engl. 2017 Jul 3;56(28):8153-8157.
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