Vps34-PIK-III

1383716-40-2

C17H17N7

DMSO : >= 31 mg/mL (97.07 mM)

PI3K/Akt/mTOR; Autophagy

Vps34-PIK-III is a potent and selective inhibitor of VPS34 with an IC₅₀ of 18 nM. IC50 & Target: IC50: 18 nM (VPS34)^[1][2], 3.96 uM (PI3Kalpha), 1.2 uM (PI3Kdelta), 3.04 uM (PI3Kgamma)^[2] In Vitro: PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI3Kalpha. PIK-III is at least 100-fold-selective for VPS34 over related lipid kinases such as PI3K and the protein kinase mTOR. PIK-III acutely inhibits autophagy and de novo lipidation of LC3, and leads to the stabilization of autophagy substrates. In H4 cells expressing the mCherry-GFP-LC3 reporter PIK-III inhibits the formation of mCherry-positive autolysosomes and increases the cytosolic signal of LC3 under basal conditions and when autophagy is induced with the mTOR inhibitor AZD8055. PIK-III prevents the turnover of GFP-tagged p62 under basal conditions and when autophagy is activated. PIK-III treatment leads to an increase in the levels of LC3-I in H4 and PSN1 cells^[2]. In Vivo: The DFX-induced NCOA4-dependent turnover of FTH1 and FTL is blocked with PIK-III suggesting an autophagy-dependent process^[2].