NVP-BKM120

NVP-BKM120 is an orally bioavailable inhibitor of the class I PI3K isoforms p110α (IC₅₀ = 52 nM) and p110β (IC₅₀ = 166 nM).¹ 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).^2,3 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.⁴ 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.²

WARNING This product is not for human or veterinary use.

1. Maira, S.M., Pecchi, S., Huang, A., et al. Identification and characterization of NVP-BKM120, an orally available pan-class I PI3-kinase inhibitor. Mol. Cancer Ther. 11(2), 317-328 (2012).

2. Koul, D., Fu, J., Shen, R., et al. Antitumor activity of NVP-BKM120--a selective pan class I PI3 kinase inhibitor showed differential forms of cell death based on p53 status of glioma cells. Clin. Cancer Res. 18(1), 184-195 (2012).

3. Park, E., Park, J., Han, S.W., et al. NVP-BKM120, a novel PI3K inhibitor, shows synergism with a STAT3 inhibitor in human gastric cancer cells harboring KRAS mutations. Int. J. Oncol. 40(4), 1259-1266 (2012).

4. de Gooijer, M.C., Zhang, P., Buil, L.C.M., et al. Buparlisib is a brain penetrable pan-PI3K inhibitor. Sci. Rep. 8(1), 10784 (2018).