Home>>Signaling Pathways>> PI3K/Akt/mTOR Signaling>> PI3K>>BYL-719

BYL-719 (Synonyms: BYL 719; BYL719)

Catalog No.GC16462

BYL-719 (BYL-719) is a potent, selective, and orally active PI3Kα inhibitor. BYL-719 (BYL-719) shows efficacy in targeting PIK3CA-mutated cancer. BYL-719 (BYL-719) also inhibits p110α/p110γ/p110δ/p110β with IC50s of 5/250/290/1200 nM, respectively. Antineoplastic activity.

Products are for research use only. Not for human use. We do not sell to patients.

BYL-719 Chemical Structure

Cas No.: 1217486-61-7

Size Price Stock Qty
5mg
$42.00
In stock
10mg
$56.00
In stock
50mg
$84.00
In stock
100mg
$133.00
In stock
200mg
$238.00
In stock
500mg
$553.00
In stock
1g
$885.00
In stock

Tel:(909) 407-4943 Email: sales@glpbio.com

Customer Reviews

Based on customer reviews.

  • GlpBio Citations

    GlpBio Citations
  • Bioactive Compounds Premium Provider

    Bioactive Compounds Premium Provider

Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Cell experiment [1]:

Cell lines

Rhabdomyosarcoma cell line(RD,SJCRH30 and A204)

Preparation Method

BYL-719 was dissolved in DMSO,to generate a stock solution (10 mM) which was subsequently diluted with the medium before adding to the cells. Rhabdomyosarcoma cell line were treated with BYL-719, then cell viability was evaluated by MTT assay.

Reaction Conditions

Rhabdomyosarcoma cell line were treated with BYL-719 (0-20μM) for 72 h.

Applications

BYL-719 decrease the viability of rhabdomyosarcoma(RMS) cell lines.BYL-719 treatment significantly affected cell proliferation of all the Rhabdomyosarcoma cell lines tested, confirming that PI3Kɑ was one of the isoforms expected to be involved in sustaining RMS cell proliferation.

Animal experiment [2]:

Animal models

Wild-type FVB/N mice, c-Met/H1047R mice

Preparation Method

BYL-719 was administered daily by oral gavage.Treatments were performed for 3 consecutive weeks after moderate tumor burden occurred.

Dosage form

25mg/kg/day, oral gavage

Applications

BYL-719 suppressed HCC angiogenesis in all the mouse models tested. BYL-719-treated mice were alive and in relatively good conditions when harvested after 3 weeks of treatment.Lliver weight in the BYL-719 cohort was lower than that from the vehicle cohort and similar to that of pretreatment tumor burden.

References:

[1]. Piazzi M, Bavelloni A, et al. Combined Treatment with PI3K Inhibitors BYL-719 and CAL-101 Is a Promising Antiproliferative Strategy in Human Rhabdomyosarcoma Cells. Molecules. 2022 Apr 24;27(9):2742.

[2]. Xu H, Chen K, et al. Alpelisib combination treatment as novel targeted therapy against hepatocellular carcinoma. Cell Death Dis. 2021 Oct 8;12(10):920.

Background

BYL719 (Alpelisib) is a selective PI3Kɑ inhibitor.It induced fewer toxicities and had a more favorable safety profile compared to a pan class I PI3K inhibitor.PI3K/AKT and mTOR pathways regulate several processes involved in cell survival, protein synthesis, cell proliferation and differentiation, metabolism, senescence, motility, and angiogenesis.Results from preclinical studies show that BYL719 inhibits PI3K signaling and prevents AKT phosphorylation in cell lines harboring PIK3CA mutations, and blocks tumor growth in xenograft models[1].

BYL-719 treatment induced G0/G1 cell cycle arrest irrespective of PIK3CA mutational status. Notably, in PIK3CA-mutant cells (AGS and MKN1), sub-G1 fraction remarkably increased (p < 0.05), suggesting increased apoptosis by BYL-719 in these cell lines. BYL-719 in combination with paclitaxel demonstrated synergistic anti-proliferative effects, preferentially in PIK3CA-mutant GC cells, resulting in increased DNA damage response and apoptosis[2].

In mouse xenograft model of PIK3CA-mutant MKN1 GC cells, BYL-719 (25mg/kg/day) combined with paclitaxel (20mg/kg/day) significantly enhanced anti-tumor activity by decreasing Ki-67 expression and increasing TUNEL expression. Moreover, this combination prolonged the survival of tumor-bearing mice during 4 weeks of treatment period without resulting in significant change in body weight[2].

Oral consumption of BYL-719 results in dose-dependent hyperglycemia and hyperinsulinemia. Littermates were block-randomised to receive either the diet containing either 0.3 g/kg BYL-719. Following 6 weeks of treatment higher fed blood glucose and plasma insulin levels were evident in the BYL-719 treated groups, and a trend towards decreased body weight was seen with BYL-719 treatment without a difference in food intake. We have previously shown that p110α inhibitors can prevent weight gain in young (4–5 weeks old) mice during development[3].

BYL-719 reduces obesity and elevates energy expenditure in mice.The most dramatic on-target effect of BYL-719 was hyperglycemia, which in the case of the ob/ob mice was severe due to their diabetic condition.However, it is important to note that in normal lean mice, the glycemia induced by PI3Kɑ inhibition is within physiological range [4].

References:
[1].Ando Y, Iwasa S, et al. Phase I study of alpelisib (BYL719), an α-specific PI3K inhibitor, in Japanese patients with advanced solid tumors. Cancer Sci. 2019 Mar;110(3):1021-1031.
[2].Kim KJ, Kim JW, et al. PI3K-targeting strategy using alpelisib to enhance the antitumor effect of paclitaxel in human gastric cancer. Sci Rep. 2020 Jul 23;10(1):12308.
[3].Hedges CP, Pham T, et al. Prolonged treatment with a PI3K p110α inhibitor causes sex- and tissue-dependent changes in antioxidant content, but does not affect mitochondrial function. Biosci Rep. 2020 Oct 30;40(10):BSR20201128.
[4].Lopez-Guadamillas E, Muñoz-Martin M, et al. PI3Kα inhibition reduces obesity in mice. Aging (Albany NY). 2016 Nov 4;8(11):2747-2753.

Chemical Properties

Cas No. 1217486-61-7 SDF
Synonyms BYL 719; BYL719
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
Canonical SMILES CC1=C(SC(=N1)NC(=O)N2CCCC2C(=O)N)C3=CC(=NC=C3)C(C)(C)C(F)(F)F
Formula C19H22F3N5O2S M.Wt 441.47
Solubility ≥ 22.1mg/mL in DMSO Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 2.2652 mL 11.3258 mL 22.6516 mL
5 mM 0.453 mL 2.2652 mL 4.5303 mL
10 mM 0.2265 mL 1.1326 mL 2.2652 mL
  • Molarity Calculator

  • Dilution Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
**When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / CoA (available online).

Calculate

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

mg/kg g μL

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO % % Tween 80 % ddH2O
%DMSO %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.

Reviews

Review for BYL-719

Average Rating: 5 ★★★★★ (Based on Reviews and 32 reference(s) in Google Scholar.)

5 Star
100%
4 Star
0%
3 Star
0%
2 Star
0%
1 Star
0%
Review for BYL-719

GLPBIO products are for RESEARCH USE ONLY. Please make sure your review or question is research based.

Required fields are marked with *

You may receive emails regarding this submission. Any emails will include the ability to opt-out of future communications.