SAR405 is a potent kinase inhibitor of PI3K class III (PIK3C3), highly specific on VPS34 (with IC50 value of 1 nM and Kd value of 1.5 nM for PIK3C3/VPS34). This compound has an exquisite protein and lipid kinase selectivity profile that is explained by its unique binding mode and molecular interactions within the ATP binding cleft of human Vps34. Inhibition of Vps34 kinase activity by SAR405 affects both late endosome-lysosome compartments and prevents autophagy. Concomitant inhibition of Vps34 and mTOR, with SAR405 and mTOR inhibitor everolimus (Axon 4149), results in synergistic antiproliferative activity in renal tumor cell lines.

KEYWORDS: SAR405 | VPS34 inhibitor | PI3K inhibitor | SAR 405 | SAR-405 | CAS [1523406-39-4] |  Phosphatidylinositol | PI3K | Inhibitor | Enzymes | Vsp34 | PI3K(class III) | Autophagy | PIK3C3 | Kinase