Name: BYL-719
Price: 260.00 USD

- Overview
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    Background
    
    BYL719 is a selective PI3Kα inhibitor with IC50 of 5 nM. It has minimal effect on PI3Kβ, γ and δ[1]. Dysregulation of the PI3K signaling pathway is involved in multiple cancers. Among genes encoding different PI3K catalytic subunits, PIK3CA is mutated in many cancers. Therefore, PI3Kα-specific inhibitor may have anti-tumor activity in PI3Kα mutant cancers with fewer side effects compared to other pan-PI3K inhibitors.
    BYL719 exhibited favorable pharmacokinetics and excellent oral bioavailability in animal models. In xenografts using nude mice, it showed dose-dependent effect of tumor inhibition[1]. It reduced proliferation and induced apoptosis in multiple myeloma cells which have higher expression of PIK3CA. The same study also observed synergistic effect between BYL719 and bortezomib or carfilzomib[2].
    Clinical data suggests a disable safety profile with manageable side effects for BYL719. It also showed preliminary anti-tumor activity as a single agent in cancer patients[3]. This compound is currently tested in several clinical studies both as single agent and in combination with other agents.
    
    1. Furet P, Guagnano V, Fairhurst RA et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett 2013; 23: 3741-3748.
    2. Azab F, Vali S, Abraham J et al. PI3KCA plays a major role in multiple myeloma and its inhibition with BYL719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance. Br J Haematol 2014; 165: 89-101.
    3. Juric D, Argiles G, Burris H et al. Phase I study of BYL719, an alpha-specific PI3K inhibitor, in patients with PIK3CA mutant advanced solid tumors: preliminary efficacy and safety in patients with PIK3CA mutant ER-positive (ER+) metastatic breast cancer (MBC). Cancer Res 2012; 72: P6-10.
- Properties
  - Alternative Name
    
    BYL 719; BYL719; (2S)-1-N-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl]-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide
    
    CAS Number
    
    1217486-61-7
    
    Molecular Formula
    
    C19H22F3N5O2S
    
    Molecular Weight
    
    441.47
    
    Appearance
    
    A solid
    
    Purity
    
    99.57%
    
    Solubility
    
    ≥22.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. A Thole, B Thibault, et al. "The lipid kinase PI3Kα is required for aggregation and survival of intraperitoneal cancer cells." bioRxiv. 2019 September 23.
    2. Chen H, Wong CC, et al. "APLN promotes hepatocellular carcinoma through activating PI3K/Akt pathway and is a druggable target." Theranostics. 2019 Jul 9;9(18):5246-5260. PMID:31410213
    3. White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
    4. Han MW, Ryu IS, et al."Phosphorylation of PI3K regulatory subunit p85 contributes to resistance against PI3K inhibitors in radioresistant head and neck cancer." Oral Oncol. 2018 Mar;78:56-63. PMID:29496059