Alpelisib

SKU: orb1307105

Description

Alpelisib (BYL-719) is an orally bioavailable, potent, and selective PI3Kα inhibitor (IC50=5 nM) with significantly lower activity against other PI3K isoforms. It demonstrates antitumor efficacy in both in vitro and in vivo models, specifically targeting cancers harboring PIK3CA mutations.

Research Area

Signal Transduction

Key Properties

• CAS Number: 1217486-61-7
• MW: 441.47
• Purity: 99.73%
• Formula: C₁₉H₂₂F₃N₅O₂S
• SMILES: Cc1nc(NC(=O)N2CCC[C@H]2C(N)=O)sc1-c1ccnc(c1)C(C)(C)C(F)(F)F
• Target: PI3K
• Solubility: Ethanol:2 mg/mL (4.53 mM);DMSO:240 mg/mL (543.64 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:8.2 mg/mL (18.57 mM)

Bioactivity

• Target IC50:
  p110δ:290 nM|p110α:5 nM (cell free)|p110α-E545K:4 nM|p110γ:250 nM (cell free)|p110α-H1047R:4 nM|p110β:1200 nM
• In Vivo:
  METHODS: To assay anti-tumor activity in vivo, Alpelisib (12.5-50 mg/kg, methylcellulose 0.5%) was administered orally to Rj:NMRI-nude mice bearing human osteosarcoma HOS-MNNG once daily for twenty-two days. RESULTS: Alpelisib significantly reduced tumor volume in a dose-dependent manner. METHODS: To investigate the modulatory effects on collagen, Alpelisib (12.5-50 mg/kg) was administered orally to nude mice bearing subcutaneous xenografts of Rat1-myr-p110α tumors once daily for eight days. RESULTS: Treatment with 12.5, 25, and 50 mg/kg of Alpelisib was well tolerated and produced dose-dependent and statistically significant antitumor effects with a T/C of 14.1% and regressions of 9.6% and 65.2%, respectively.
• In Vitro:
  METHODS: Osteosarcoma cell lines MG-63, HOS, MOS-J and POS-1 were treated with Alpelisib (0-50 µM) for 72 h and cell viability was measured using XTT assay. RESULTS: Alpelisib significantly inhibited cell growth of all osteosarcoma cell lines in a dose-dependent manner with IC50 ranging from 6-15 µM and IC90 ranging from 24-42 µM. METHODS: PIK3CA wild-type cells (SNU638 and SNU668) and three PIK3CA mutant cells (SNU601, AGS, and MKN1) were treated with Alpelisib (5 µM) for 24 h, and cell cycle profiles were examined using Flow cytometry. RESULTS: Alpelisib treatment induced G0/G1 cell cycle arrest regardless of PIK3CA mutation status. In PIK3CA mutant cells (AGS and MKN1), there was a significant increase in the sub-G1 fraction, suggesting that Alpelisib increased apoptosis in these cell lines.
• Cell Research:
  To evaluate the isoform-specific potency of NVP-BYL719 in a cell-based system, an N-terminally myristoylated form of each PI3K class IA isoform was expressed in Rat1 fibroblasts. The retroviral expression plasmid pBabePuro containing human p110α, p110β, and p110δ with an N-terminal myristoylation (myr) signal followed by an HA-tag were generated. Successfully infected Rat1 cells were selected in medium containing 4 μg/mL of puromycin, expanded and characterized for expression of the p110 isoforms. Transgenic expression of the myristoylated protein was confirmed by increased levels of phosphorylated Akt .
• Animal Research:
  All in life experimentation and efficacy studies were conducted as described previously. Tumor xenografts were grown subcutaneously or orthotopically in nude mice or nude Rowett rats (Hsd: RH-Fox1rnu) by injection of 3 × 10^6 to 1 × 10^7 cells or implantation of tumor fragments of approximately 50 mg. Tumor-bearing animals mice were treated with either vehicle control, NVP-BYL719, or NVP-BKM120 (p.o., every day) at the doses indicated .

Storage & Handling

• Storage: store at low temperature | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, mutant, inhibit, metastasis, breast, antineoplastic, cancer, BYL 719, BYL719, BYL-719, Alpelisib, AKT, Phosphoinositide 3-kinase, PI3K, phosphorylation, PIK3CA, PI3Kα, p110α

Compound Identifiers

PubChem CID

56649450