Alpelisib

Alpelisib (BYL-719) is a potent, selective, and orally active PI3Kα inhibitor. Alpelisib (BYL-719) shows efficacy in targeting PIK3CA-mutated cancer. Alpelisib (BYL-719) also inhibits p110α/p110γ/p110δ/p110β with IC₅₀s of 5/250/290/1200 nM, respectively. Antineoplastic activity^[1][2][3]. IC50 & Target: IC50: 5 nM (p110α), 250 nM (p110γ), 290 nM (p110δ), 1200 nM (p110β)^[1] In Vitro: Alpelisib (BYL-719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC₅₀s~4 nM). Alpelisib potently inhibits Akt phosphorylation in cells transformed with PI3Kα (IC₅₀=74±15 nM) and shows significant reduced inhibitory activity in PI3Kβ or PI3Kδ isoforms transformed cells (≥15-fold compared with PI3Kα)^[2].
Alpelisib (BYL-719, 0-50 μM; 72 hours) inhibits the cell growth of osteosarcoma cell lines MG63, HOS, POS-1 and MOS-J in a dose-dependent manner^[3].
Alpelisib (BYL-719) significantly alters the distribution of cell cycle phases. Alpelisib (BYL-719, 25 μM; 18 hours) induces a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell lines^[3].
In Vivo: Alpelisib (BYL-719) (12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice; oral administration; daily) significantly reduces tumor volumes and deposition of ectopic bone matrix^[3].
Alpelisib has moderate terminal elimination half-life (t_1/2=2.9±0.2 h) for rat (1 mg/kg, iv) ^[1].