PI-103 is a cell-permeable pyridinylfuranopyrimidine compound that acts as an ATP-competitive inhibitor of DNA-PK, PI 3-kinase (Class IA), and FRAP (mTOR) complex 1 and 2. Studies suggest that PI-103 can induce apoptosis and an arrest in the cell cycle by inhibition of the aforementioned proteins. When PI-103 is combined with rapamycin, a prototypic mTORC1 inhibitor, synergistic suppression of AKT and ribosomal S6 protein phosphorylation are observed. In addition, PI-103 has been seen to have nominal effects inhibiting basal Na+ transport, but is very effective in abolishing insulin-induced Na+ absorption in the nephron.
