BYL-719

Research use only, not for human use.

Alpelisib (BYL-719) is a potent and selective PI3Kα inhibitor with IC50 of 5 nM in a cell-free assay, and minimal effect on PI3Kβ/γ/δ. Phase 2.

Alpelisib (BYL-719) is a potent and selective PI3Kα inhibitor with IC50 of 5 nM in a cell-free assay, and minimal effect on PI3Kβ/γ/δ. Phase 2.(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).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.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.(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.Alpelisib has moderate terminal elimination half-life (t1/2=2.9±0.2 h) for rat (1 mg/kg, iv) .

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Animal Model:A 5-week-old female Rj:NMRI-nude mice withhuman HOS-MNNG osteosarcoma cells; A 5-week-old male C57Bl/6J mice with mouse MOS-J osteosarcoma cells Dosage:12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice Administration:Oral administration; daily; 22 or 29 days for C57Bl/6J mice or Rj:NMRI-nude mice Result:Significantly reduced tumor volumes and simultaneously reduced tumor growth.Animal Model:Female Sprague Dawley rats Dosage:1 mg/kg (Pharmacokinetic Analysis)Administration:I.V.Result:t1/2=2.9±0.2 hours.

Alpelisib

PI3K/Akt/mTOR signaling

PI3K

PI3Kα

Cancer

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1217486-61-7

441.47

C19H22F3N5O2S

>98% (HPLC)

Ethanol: 2 mg/mL (4.53 mM); DMSO: 88 mg/mL (199.33 mM)

O=C(N1[C@H](C(N)=O)CCC1)NC2=NC(C)=C(C3=CC(C(C)(C)C(F)(F)F)=NC=C3)S2

(S)-N1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide.

(-20℃)

With Ice Pack

≥ 2 years