BLU9931 - FGFR 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEBLU9931Cat. No.: HY-12823CAS No.: 1538604-68-0分式: CHClNO分量: 509.38作靶点: FGFR作通路: Protein Tyrosine Kinase/RTK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 : 17 mg/mL (33.37 mM; Need ultrasoni

2、c and warming)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.91 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 (4.91 mM); Suspended solution; Need ultrasonic3. 请依序添加每种溶剂： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您边的抑制剂师www.MedChem

3、ESolubility: 2.5 mg/mL (4.91 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 BLU9931种有效的，选择性的和不可逆的 FGFR4 抑制剂，IC50 分别为3 nM。IC50 & Target FGFR1 FGFR2 FGFR3 FGFR4591 nM (IC50) 493 nM (IC50) 150 nM (IC50) 3 nM (IC50)体外研究 In MDA-MB-453 cells, BLU9931 potently inhibits phosphorylation of FGFR4 signaling pathway

4、. BLU9931inhibits proliferation of HCC cell lines that express an intact FGFR4 signaling complex, such as Hep 3B,HUH-7, and JHH-7 cell lines, with EC50 of 1. BLU9931 induces tumor shrinkage in hepatocellularcarcinoma models that express a functioning ligand/receptor complex consisting of FGF19/FGFR4

5、/KLB andadds to a growing list of anti-FGFR4 agents 2.体内研究 BLU9931 (300 mg/kg, p.o.) leads to tumor regression and prevents this weight loss in mice bearing theFGF19-amplified Hep 3B liver tumors. In mice bearing the FGF19-overexpressing PDX-derived LIXC012xenografts, treatment with BLU9931 (300 mg/

6、kg, p.o.) also leads to tumor regression 1.PROTOCOLKinase Assay 1 FGFR kinase inhibition assays are performed at KM for ATP. Picomolar to low nanomolar concentrations ofFGFR proteins are incubated in 1 Kinase Reaction Buffer (KRB) with 1 M of CSKtide and 50 to 250 of MATP at 25C for 90 minutes in th

7、e presence or absence of a dosed concentration series of inhibitor. Allreactions are terminated by the addition of Stop buffer, and plates are read on a Caliper EZReader2. IC50values are fit with a four-parameter logInhibitor versus response model with floating Hill Slope.MCE has not independently c

8、onfirmed the accuracy of these methods. They are for reference only.Cell Assay 1 established and PDX-derived HCC cell lines are seeded in 96-well plates in respective growth media,allowed to attach overnight, and treated with a dilution series of test compounds for two cell-doubling times.Cell viabi

9、lity is determined by CellTiter-Glo, and results represented as background-subtracted relative lightunits normalized to a DMSO-treated control. Relative EC50 values are determined at 50% inhibition betweenthe top and bottom plateau of the dose-response curve.MCE has not independently confirmed the a

10、ccuracy of these methods. They are for reference only.Animal BLU9931 is formulated in 0.5% carboxymethylcellulose/1% Tween 80 and dosed orally as a suspensionAdministration 1 twice daily. Sorafenib is dissolved in Cremaphor:EtOH (1:1) and diluted with saline or water to yield the stocksolution. Sora

11、fenib is dosed orally once daily. All compound doses are expressed as mg/kg free base. ForPK-PD studies, 3 mice are included in each treatment group. Mice receive four doses of compound orvehicle. Blood and tumors are collected 8, 12, 20, and 24 hours following the last dose. The concentration ofBLU

12、9931 in plasma is determined by LC/MS-MS. A section of each tumor is immediately frozen in liquidnitrogen and stored at 80C.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Int J Oncol. 2017 No

13、v;51(5):1611-1620.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Hagel M, et al. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an ActivatedFGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37.2. Packer LM, et al. Paralog-Specific Kinase Inhibition of FGFR4: Adding to the Arsenal of Anti-FGFR Agents. Cancer Discov. 2015Apr;5(4):355-7.M