Description
BKM120 (NVP-BKM120) can inhibit p110-alpha, p110-beta, p110-delta and p110-gamma with IC50 of 52 nM, 166 nM, 166 nM and 262 nM.
Storage
2 years at -20centigrade Powder
Targets
p110-alpha, p110-beta, p110-delta, p110-gamma
Molecular Formula
C18H21F3N6O2
Chemical Name
5-(2,6-dimorpholinopyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine
Solubility
DMSO 82 mg/mL Water
In vitro
2-morpholino pyrimidine derivative pan-PI3K inhibitor, NVP-BKM120, can inhibit all four class I PI3K isoforms with at least 50-fold selectivity against other protein kinases, but does not significantly inhibit the related class III (Vps34) and class IV (mTOR, DNA-PK) PI3K kinases. As a selective PI3K inhibitor, NVP-BKM120 can decreases the cellular levels of p-Akt in mechanistic models and relevant tumor cell lines and block the PI3K/Akt signaling cascade leading to a dose-dependent growth inhibition. BKM120 can cause cell death in various cellular systems, irrespective of their level of PI3K addiction. BKM120 also inhibited microtubule dynamics upon direct binding to tubulin. At 5 to 10-fold the concentration needed to half-maximally inhibit PI3K signaling, BKM120 treatment caused changes in expression of mitotic genes and the induction of a robust G2/M arrest. NVP-BKM120 and p53 There is a relationship between the cell lines sensitivity to NVP-BKM120 and p53 status in glioma cells with different p53 status. Actually, glioma cells containing wild-type p53 are more sensitive to NVP-BKM120 than cells with mutated or deleted p53.NVP-BKM120 showed differential forms of cell death on the basis of p53 status of the cells with p53 wild-type cells undergoing apoptotic cell death and p53 mutant/deleted cells having a mitotic catastrophe cell death.
In vivo
NVP-BKM120 inhibits the PI3K pathway in tumor-bearing animals and displays strong antitumor activity in vivo. Rat1-myr-p110alpha tumor-bearing animals were treated orally, once, at dose levels of either 30 or 60 mg/kg. Maximum inhibition of p-Akt levels in tumor tissue was achieved at the 1 hour time point.
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