Alpelisib 1217486-61-7

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Synonyms

：

Appearance

：

white powder

Chemical Formula

：

C19H22F3N5O2S

Solubility

：

Molecular Weight

：

441.47

Storage and Stability

：

in stock

CAS No.

：

1217486-61-7

Purity

：

99.5%

Introduction

BYL-719 is a potent and selective PI3Kα inhibitor with IC₅₀ of 5 nM. IC50 & Target: IC50: 5 nM (p110α), 250 (p110γ), 290 (p110δ), 1200 (p110β) In Vitro: BYL-719 (NVP-BYL719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K; IC₅₀～4 nM). BYL-719 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). BYL-719 (BYL719) decreases cell proliferation by blocking cell cycle in G₀/G₁ phase with no outstanding effects on apoptosis cell death in HOS and MOS-J tumor cells. BYL-719 inhibits cell migration and can thus be considered as a cytostatic drug for osteosarcoma. In murine preclinical models of osteosarcoma, BYL-719 significantly decreases tumor progression and tumor ectopic bone formation as shown by a decrease of Ki67⁺ cells and tumor vascularization. BYL-719 rapidly inhibits the levels of P-AKT and P-mTOR in all cell lines assessed, confirming the functional activity of BYL-719 on osteosarcoma cells. After 72 hr of treatment, BYL-719 significantly inhibits the cell growth of all osteosarcoma cell lines tested in a dose-dependent manner with an IC₅₀ ranging from 6 to 15 μM and with the IC₉₀ from 24 to 42 μM at 72 hr. In Vivo: BYL-719 displays excellent oral bioavailability in rats, mice and dogs and does not show any significant inhibition of the CYP450 enzymes. BYL-719 (BYL719) inhibits tumor growth in pre-clinical murine models of osteosarcoma. C57Bl/6J with MOS-J tumors (n=6 per group) are randomized as controls (vehicle) or BYL-719 (12.5 mg/kg or 50 mg/kg per day).

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