XL147 is an orally-available, reversible and competitive ATP inhibitor of the PI3K class of kinases with potencies of 39 nM, 36 nM, and 23 nM, for isoforms PI3Ka, PI3Kd, PI3Kg, respectively. [1] It is highly selective versus mTOR (>15000 nM) and DNA-PK (4750 nM). and a broad panel of >130 human protein kinases. In cellular assays, XL147 acts as an antagonist on the production of the second messenger phosphatidylinositol-3,4,5-triphosphate (PIP3), resulting in dose-dependent downstream inhibition of phosphorylation of Akt, ribosomal S6K, and ribosomal S6 protein. [1] In MCF7 and PC-3 cell lines, XL147 inhibits pAkt (T308) at 942 and 400 nM, respectively, and inhibits pAkt (S473) at 596 and 310 nM, respectively.

XL147 has been studied as a potentiator of antitumor efficacy of paclitaxel and carboplatin without increased toxicity. [2] XL147 also works synergistically with EGFR inhibitors such as erlotinib. [3]