ASP5878 - FGFR 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEASP5878Cat. No.: HY-19983CAS No.: 1453208-66-6分式: CHFNO分量: 407.37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 : 250 mg/mL (613.69 mM)H2O : 40% PEG3

2、00 5% Tween-80 45% salineSolubility: 2.08 mg/mL (5.11 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.08 mg/mL (5.11 mM); Clear solution1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 ASP5878具有服活性的、FGFR 1、2、3、和 4 的抑制剂，其对FGFR 1、2、3、和 4 激酶的 IC50 值分别为0.47 nM、

3、0.6 nM、0.74 nM 和 3.5 nM。ASP5878 具有潜在的抗肿瘤活性。IC50 & Target FGFR1 FGFR2 FGFR3 FGFR40.47 nM (IC50) 0.6 nM (IC50) 0.74 nM (IC50) 3.5 nM (IC50)体外研究 ASP5878 shows potent antiproliferative activity in most human HCC cell lines 1.ASP5878 inhibits FGFR4 phosphorylation in a concentration-dependent manner. ASP

4、5878 treatment resultsin the suppression of phosphorylation, mobility shift of FRS2, and suppression of ERK phosphorylation 1.Cell Viability Assay 1Cell Line: Human HCC cell lines.Concentration: 0-1000 nM.Incubation Time: 5 days.Result: HuH-7, Hep3B2.1-7, and JHH-7 cell lines exhibited potent sensit

5、ivity to ASP5878, withIC50 values of 27, 8.5, and 21 nmol/L, respectively.The growth inhibition rate of HLF was 64% and those of other ASP5878-sensitive celllines were higher than 95% at 1000 nM.体内研究ASP5878 (3 mg/kg, orally, once daily) shows antitumor activity in a Hep3B2.1-7 subcutaneous xenograft

6、 andHCC orthotopic xenograft mouse model 1.ASP5878 induces shrinkage of FGF19-expressing HCC xenograft model 1.Animal Model: Four-week-old male nude mice (CAnN.Cg-Foxn1nu/CrlCrlj nu/nu) (Hep3B2.1-7 cellsinoculated subcutaneously) 1.Dosage: 3 mg/kg.Administration: Orally once daily from days 14 to 52

7、.Result: Induced tumor regression by 9% and 88% at 1 and 3 mg/kg, respectively, withoutaffecting the body weight for 14 days.Induced the suppression of FGFR4 phosphorylation, mobility shift of FRS2, andsuppression of ERK phosphorylation.Animal Model: HCC orthotopic xenograft model (mouse) 1.Dosage:

8、3 mg/kg.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEAdministration: Orally once daily for 24 days.Result: Exhibited a lower tumor burden than vehicle- and sorafenibtreated mice.Induced sustained tumor regression without tumor regrowth.REFERENCES1. Futami T, et al. ASP5878, a Novel Inhibitor of FGFR1, 2, 3, and 4, Inhibits the Growth of FGF19-Expressing Hepatocellular Carcinoma.Mol Cancer Ther. 2017 Jan;16(1):68-75.McePdfHeightCaution: Product has not been fully validated for medical applic