Size | Price | |
---|---|---|
100mg | ||
250mg | ||
500mg |
Alpelisib HCl (BLY-719; trade name: Piqray) is a novel, potent, newly approved, orally bioavailable phosphatidylinositol 3-kinase (PI3K) inhibitor with antineoplastic activity. As of May 2019, it has been approved by FDA as the first PI3K inhibitor to treat postmenopausal women, and men, with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer (as detected by an FDA-approved test) following progression on or after an endocrine-based regimen. PI3K inhibitor BYL719 specifically inhibits PIK3 in the PI3K/AKT kinase (or protein kinase B) signaling pathway, thereby inhibiting the activation of the PI3K signaling pathway. This may result in inhibition of tumor cell growth and survival in susceptible tumor cell populations. Activation of the PI3K signaling pathway is frequently associated with tumorigenesis. Dysregulated PI3K signaling may contribute to tumor resistance to a variety of antineoplastic agents. Clinical data suggests a disable safety profile with manageable side effects for BYL719.
ln Vitro |
Alpelisib (BYL-719) effectively suppresses the 2 most prevalent PIK3CA somatic mutations (H1047R, E545K; IC50s~4 nM). Alpelisib potently suppresses Akt phosphorylation in PI3Kα-transformed cells (IC50=74±15 nM) and demonstrates significantly lower inhibitory efficacy (≥15-fold relative to PI3Kα) in PI3Kβ or PI3Kδ isoform-transformed cells [2] . Alpelisib (BYL-719, 0-50 μM; 72 hours) suppresses cell proliferation in the osteosarcoma cell lines MG63, HOS, POS-1 and MOS-J in a dose-dependent manner [3]. Alpelisib (BYL-719) drastically affects the distribution of cell cycle phases. Alpelisib (BYL-719, 25 μM; 18 hours) promotes cell cycle arrest in the G0/G1 phase in human and murine osteosarcoma cell lines [3].
|
---|---|
ln Vivo |
Alpelisib (BYL-719) decreases tumor volume and ectopic bone matrix deposition considerably when administered orally once a day (12.5 mg/kg and 50 mg/kg in C57Bl/6J mice; 50 mg/kg in female Rj:NMRI nude mice)[3]. In rats, alpelisib (1 mg/kg, intravenous administration) has an intermediate terminal elimination half-life (t1/2=2.9±0.2 h)[1].
|
Cell Assay |
Cell proliferation assay[3]
Cell Types: MG63, HOS, POS-1, MOS-J Tested Concentrations: 10, 20, 30, 40, 50 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of cell growth of all osteosarcoma cell lines tested In a dose-dependent manner, IC50 is 6-15 µM and IC90 is 24-42 µM. Cell cycle analysis [3] Cell Types: MG63, HOS, POS-1, MOS-J Tested Concentrations: 25 μM Incubation Duration: 18 hrs (hours) Experimental Results: The cell cycle of human and mouse osteosarcoma cells was induced to arrest in the G0/G1 phase. |
Animal Protocol |
Animal/Disease Models: 5weeks old female Rj:NMRI nude mice, human HOS-MNNG osteosarcoma cells; 5weeks old male C57Bl/6J mice, mouse MOS-J osteosarcoma cells [3]
Doses: C57Bl/6J mice 12.5 mg/kg and 50 mg/kg; female Rj: NMRI nude mice 50 mg/kg. Route of Administration: oral; daily Experimental Results: tumor volume was Dramatically diminished, and tumor growth was also diminished. Animal/Disease Models: Female Sprague Dawley rats [1] Doses: 1 mg/kg (pharmacokinetic/PK/PK study) Route of Administration: IV Experimental Results: T1/2=2.9±0.2 hrs (hrs (hours)). |
References |
[1]. Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8.
[2]. Fritsch C, et al. Characterization of the novel and specific PI3Kα inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29. [3]. Gobin B, 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. |
Molecular Formula |
C19H23CLF3N5O2S
|
---|---|
Molecular Weight |
477.93
|
CAS # |
1584128-91-5
|
Related CAS # |
Alpelisib;1217486-61-7
|
Appearance |
Typically exists as solids (or liquids in special cases) at room temperature
|
SMILES |
CC1N=C(NC(N2CCC[C@H]2C(=O)N)=O)SC=1C1=CC=NC(C(C)(C)C(F)(F)F)=C1.Cl
|
HS Tariff Code |
2934.99.9001
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
---|---|
Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80: Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 :Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.0924 mL | 10.4618 mL | 20.9236 mL | |
5 mM | 0.4185 mL | 2.0924 mL | 4.1847 mL | |
10 mM | 0.2092 mL | 1.0462 mL | 2.0924 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.