BYL-719
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.
References:
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.
- 1. Meiping Chang, Steven Huhn, et al. "Estrogen Effects Differ Between Medium Maintenance and Replacement from Transcriptional and Clinical Perspectives in T47D Breast Cancer Cells." Anticancer Res. 2023 Oct;43(10):4447-4469. PMID: 37772550
- 2. Hye-Min Jeon, Jeong-Yub Kim, et al. "Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling." Cancer Cell. 2023 Jul 11;S1535-6108(23)00217-9. PMID: 37451272
- 3. A Thole, B Thibault, et al. "The lipid kinase PI3Kα is required for aggregation and survival of intraperitoneal cancer cells." bioRxiv. 2019 September 23.
- 4. 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
- 5. 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
- 6. 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
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 441.47 |
| Cas No. | 1217486-61-7 |
| Formula | C19H22F3N5O2S |
| Synonyms | BYL 719; BYL719 |
| Solubility | ≥22.07 mg/mL in DMSO; insoluble in H2O; insoluble in EtOH |
| Chemical Name | (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 |
| SDF | Download SDF |
| Canonical SMILES | CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment [1]: | |
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Cell lines |
Multiple myeloma cells (OPM1, OPM2, RPMI8226, U266, MM1s,MM1R) and NCI-H9290 |
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Preparation method |
Limited solubility. General tips for obtaining a higher concentration: Please warm the tube at 37°C for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months. |
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Reaction Conditions |
37°C |
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Applications |
BYL719 prominently decreases the activation of the PI3K signaling proteins (pAKT, pS6R, and pGSK), this effect are also observed in slico that BYL719 decreases the expression of the PI3K signaling proteins in a dose-dependent manner. Furthermore, BYL719 dose-dependently triggers G1 arrest and induces apoptosis in MM cells. |
| Animal experiment [2]: | |
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Animal models |
5-week-old male C57Bl/6J mice transplanted with human osteoblastic osteosarcoma |
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Dosage form |
Oral administration, 12.5–50 mg/kg daily |
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Applications |
BYL719 significantly reduces tumor volumes in a dose-dependent manner and reduces the tumor ectopic bone. In addition, BYL719 decreases the surface of TRAP+ osteoclasts without affecting the number of osterix+ cells. Moreover, BYL719 decreases of KI67+ cell number and reduces tumor vascularization. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: 1. Azab F, Vali S, Abraham J, Potter N 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 Apr;165(1):89-101. 2. Gobin B, Huin MB, Lamoureux F et al. BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-96. |
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| Description | BYL719 is a potent and selective inhibitor of PI3Kα with IC50 of 5 nM. | |||||
| Targets | PI3Kα | |||||
| IC50 | 5 nM | |||||
Quality Control & MSDS
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