Alpelisib hydrochloride (BYL-719 hydrochloride) exhibits anticancer properties[1][2]. As a potent, selective PI3Kα inhibitor with high oral bioavailability, it demonstrates IC50 values of 5 nM for p110α, 250 nM for p110γ, 290 nM for p110δ, and 1200 nM for p110β, indicating its efficacy in targeting specific enzymes involved in cancer cell proliferation.

Alpelisib (BYL-719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC50s~4 nM). 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]. 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 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 has moderate terminal elimination half-life (t1/2=2.9±0.2 h) for rat (1 mg/kg, iv)[1]. 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].