Alpelisib hydrochloride (BYL-719 hydrochloride) exhibits anticancer properties[1][2]. As a potent and selective PI3Kα inhibitor with high oral bioavailability, it has 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 enzymes involved in cancer cell proliferation.

Alpelisib (BYL-719) potently inhibits the two most common PIK3CA somatic mutations (H1047R, E545K; IC50s~4 nM) and significantly alters the distribution of cell cycle phases. At 25 μM for 18 hours, it induces a G0/G1 phase cell cycle arrest in human and murine osteosarcoma cell lines[3]. Additionally, Alpelisib (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]. In cells transformed with PI3Kα, it potently inhibits Akt phosphorylation (IC50=74±15 nM) and shows significantly reduced inhibitory activity in PI3Kβ or PI3Kδ isoform-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].