Biological Activity
Vps34-PIK-III is a potent and selective inhibitor of VPS34 with an IC50 of 18 nM.
In Vitro
PIK-III is a selective inhibitor of VPS34 that binds a unique hydrophobic pocket not present in related kinases such as PI3Kα. 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 leadsto 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].
References & source
Published experimental findings depend on the model and assay conditions. They do not guarantee equivalent performance in every application. For laboratory research use only.