Alpelisib-BYL-719-DataSheet-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAlpelisibCat. No.: HY-15244CAS No.: 1217486-61-7Synonyms: BYL-719分式: CHFNOS分量: 441.47作靶点: PI3K作通路: PI3K/Akt/mTOR储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 100 mg/mL (226.52 mM)* means

2、soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.2652 mL 11.3258 mL 22.6516 mL5 mM 0.4530 mL 2.2652 mL 4.5303 mL10 mM 0.2265 mL 1.1326 mL 2.2652 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现

3、现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.66 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (5.66 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChe

4、mE3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.66 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 Alpelisib (BYL-719)是有效，选择性的 PI3K 抑制剂，抑制 p110/p110/p110/p110 的 IC50s 分别为5 nM，250 nM，290 nM，1200 nM 。IC50 & Target p110 p110 p110 p1105 nM (IC50) 250 nM (IC50) 290 nM (IC50) 1200 nM (IC50)p110-H1

5、047R p110-E545K4 nM (IC50) 4 nM (IC50)体外研究 Alpelisib (BYL-719) potently inhibits the 2 most common PIK3CA somatic mutations (H1047R, E545K;IC50s4 nM). Alpelisib potently inhibits Akt phosphorylation in cells transformed with PI3K (IC50=7415nM) and shows significant reduced inhibitory activity in PI3

6、K or PI3K isoforms transformed cells (15-foldcompared with PI3K) 2.Alpelisib (BYL-719, 0-50 M; 72 hours) inhibits the cell growth of osteosarcoma cell lines MG63, HOS, POS-1 and MOS-J in a dose-dependent manner 3.Alpelisib (BYL-719) significantly alters the distribution of cell cycle phases. Alpelis

7、ib (BYL-719, 25 M; 18hours) induces a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell lines 3.Cell Proliferation Assay 3Cell Line: MG63, HOS, POS-1, MOS-JConcentration: 10, 20, 30, 40, 50 MIncubation Time: 72 hoursResult: Inhibited the cell growth of all osteosarcoma cell

8、lines tested in a dose-dependentmanner with IC50s of 6-15 M and with IC90s of 24-42 M.Cell Cycle Analysis 3Cell Line: MG63, HOS, POS-1, MOS-JConcentration: 25 MIncubation Time: 18 hoursResult: Induced a cell cycle arrest in the G0/G1 phase of human and murine osteosarcoma cell .体内研究Alpelisib (BYL-71

9、9) (12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude mice;oral administration; daily) significantly reduces tumor volumes and deposition of ectopic bone matrix 3.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAlpelisib has moderate terminal elimination half-life (t1/2=2.

10、90.2 h) for rat (1 mg/kg, iv) 1.Animal Model: A 5-week-old female Rj:NMRI-nude mice with human HOS-MNNG osteosarcoma cells; A5-week-old male C57Bl/6J mice with mouse MOS-J osteosarcoma cells 3Dosage: 12.5 mg/kg and 50 mg/kg for C57Bl/6J mice; 50 mg/kg for female Rj:NMRI-nude miceAdministration: Oral

11、 administration; dailyResult: Significantly reduced tumor volumes and simultaneously reduced tumor growth.Animal Model: Female Sprague Dawley rats 1Dosage: 1 mg/kgAdministration: I.V.Result: t1/2=2.90.2 hours户使本产品发表的科研献 Nature. 2018 Jun;558(7711):540-546. Science. 2017 Dec 1;358(6367). Sci Transl Me

12、d. 2018 Jul 18;10(450). pii: eaaq1093. Blood. 2019 Jan 3;133(1):70-80. Cell Syst. 2019 Jul 5. pii: S2405-4712(19)30200-5.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Furet P, et al. Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor

13、selected for clinicalevaluation. Bioorg Med Chem Lett. 2013 Jul 1;23(13):3741-8.2. Fritsch C, et al. Characterization of the novel and specific PI3K inhibitor NVP-BYL719 and development of the patient stratificationstrategy for clinical trials. Mol Cancer Ther. 2014 May;13(5):1117-29.3. Gobin B, et al. BYL719, a new -specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for thetreatment of osteosarcoma. Int J Cancer. 2015 Feb 15;136(4):784-