NVP-BKM120 (Synonyms: Buparlisib)

NVP-BKM120 is an orally bioavailable inhibitor of the class I PI3K isoforms p110α (IC50 = 52 nM) and p110β (IC50 = 166 nM). It is selective for these isoforms over the class III PI3K Vps34 (IC50 = 2,410 nM), the mammalian target of rapamycin (mTOR; IC50 = 2,866 nM), PI4Kβ (IC50 = >25,000 nM), and a variety of kinases (IC50s = >10,000 nM). NVP-BKM120 inhibits proliferation of human tumor and glioma cell lines, with p53 wild-type glioma cells being more sensitive than p53 mutant/deleted glioma cells (IC50s = 1.28 and 2.08 µM, respectively). It halts the cell cycle in the G2/M phase in both p53 wild-type and p53 mutant/deleted glioma cells, but p53 mutant/deleted cells reenter the cell cycle, progress into mitosis, and die via mitotic catastrophic cell death. NVP-BKM120 (1-5 mg/kg) crosses the blood brain barrier and selectively decreases phosphorylation of the PI3K target protein Akt. It increases survival in a U87 glioma mouse xenograft intracranial tumor model when administered orally at doses of 20 and 40 mg/kg once per week.