Buparlisib: Phosphatidylinositol 3-kinase alpha inhibitor oncolytic

The PI3K signaling pathway is dysregulated in many tumor types, where it is associated with a poor prognosis and resistance to multiple therapies, and inhibition of PI3K is an emerging strategy in the treatment of cancer. Buparlisib (NVP-BKM-120) is a 2,6-dimorpholinopyrimidine derivative and a potent pan-PI3K inhibitor, inhibiting PI3K downstream signaling, including downregulation of p-Akt and p-S6R, and inducing apoptosis of cancer cells. In animal models, buparlisib inhibited tumor growth and metastasis of breast, lung, glioma, multiple myeloma, gastric and soft tissue sarcoma, and it synergized with other cytotoxic agents. Buparlisib is rapidly absorbed and highly bioavailable after oral administration, with a half-life of approximately 40 hours, mainly via hepatic clearance. The product is currently being tested in clinical trials in several solid tumors and was found to be well tolerated, preliminary data demonstrating variable clinical responses including partial response, stable disease and progressive disease.