PI-103 is a multi-targeted PI3K inhibitor for p110α/β/δ/γ with IC50 of 2 nM/3 nM/3 nM/15 nM, less potent to mTOR/DNA-PK with IC50 of 30 nM/23 nM.

The phosphatidylinositol 3-kinases (PI3K) family of enzymes is comprised of 15 members that are divided into 3 classes according to their structure, substrate specificity, and mode of regulation.PI-103 is a potent, cell-permeable, ATP-competitive inhibitor of phosphatidylinositol 3-kinase (PI3K) family members with selectivity toward DNA-PK, PI3K (p110α), and mTOR. The IC50 values are 2, 8, 20, 26, 48, 83, 88, 150 nM for DNA-PK, p110α, mTORC1, PI3-KC2β, p110δ, mTORC2, p110β, and p110γ, respectively.PI-103 exhibits antiproliferative activity against a panel of glioma cell lines in vitro at a concentration of 0.5 µM. It also inhibits growth of established human glioma tumor xenografts in vivo with no observable toxicity.