生物活性

• 靶点

  p110α IC50:52nM

  p110β IC50:166nM

  p110γ IC50:262nM

  p110δ IC50:116nM

• 描述PI3Ks (Phosphatidylinositol-4,5-bisphosphate 3-kinase) participate in a diverse array of process, including the regulation of cellular survival, differentiation and stem cell-like properties, growth, proliferation, metabolism, migration, and angiogenesis^[2]. BKM120 is an orally bioavailable pan-PI3K inhibitor with IC50 value of IC50=52nM, IC50=116nM, IC50=166nM, IC50=262nM, IC50=2.4μM, IC50=4.6μM on p110α, p110δ, p110β, p110γ(measured by filter binding assay), Vps34 (measured by ATP depletion assay), mTOR (measured by TR-FRET assay), respectively, most potent on Class I PI3Ks. Treatment of BKM120 can cause decrease of p-AKT-ser473 (downstream of PI3Ks) both in vitro and in vivo. BKM120 has good pharmacokinetic properties, exhibiting medium to high oral bioavailability across species as 80%, 50%, 44% and 100% observed in mouse, rat, dog, and monkey, respectively^[1]. For BKM120 is well-tolerated and permeable to the blood–brain barrier, it is the most frequently-used PI3K inhibitor in the clinical trials for glioblastoma multiforme treatment^[3].
• 作用机制Mechanism: BKM120 has greater affinity for the free PI3K enzyme,relative to the ATP bound.^[4]

• 动物研究
  剂量	Nude Mice: min = 2 mg/kg, max = 20 mg/kg[5] Mice: min = 30 mg/kg, max = 60 mg/kg[4]
  给药途径	p.o., i.v., i.p.