生物活性

• 靶点	PI3Kα IC50:5nM

• 描述There three kinds of catalytic subunits of Class IA PI3Ks, p110α, p110β and p110δ. One of the subunits, P110α, is encoded by PIK3CA in human, which is found to be mutated in many human cancers, for example, colorectal cancers, glioblastomas, gastric cancers, hepatocellular carcinomas, breast cancers. Alpelisib, also called as BYL719, is an orally available p110α inhibitor against with IC50 of 5 nM, less potent to p110β (IC50 = 1.2 μM), p110γ (IC50 = 0.25 μM) and PI3Kδ (IC50 = 0.29 μM, measured by biochemical assay). Alpelisib can block the PI3K/Akt signaling pathway resulting in inhibition of Akt phosphorylation in Rat1-myr-p110x cells^[1]. Alpelisib exhibits potent anti-proliferative and anti-tumor activities in lung squamous cell carcinoma (LSCC) in a PIK3CA-dependent manner^[2]. Now Alpelisib is used in phase I/II trials in patients with breast cancer, lung cancer, pancreatic cancer and squamous cell carcinoma etc.^[3].
• 作用机制Alpelisib can interact with the ATP binding pocket of p110α^[1].

• 动物研究
  剂量	Mice[4] (p.o.): 12.5 mg/kg – 50 mg/kg (daily)
  给药途径	p.o.
  动物药代数据	Animal Mice[1] Rats[1] Dogs[1] Dose 3 mg/kg 15 mg/kg 0.6 mg/kg Administration p.o. p.o. p.o. Cmax 0.52 µM (dose normal) 0.19 µM (dose normal) 1.07 µM (dose normal) BAV 1.06 0.58 1.4 CL 8 ml/min/kg 10 ml/min/kg 8 ml/mjin/kg