BLU9931

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Chemical Structure| 1538604-68-0 同义名 : -
CAS号 : 1538604-68-0
货号 : A231990
分子式 : C26H22Cl2N4O3
纯度 : 99%+
分子量 : 509.384
MDL号 : MFCD28900729
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 85 mg/mL(166.87 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 1 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • FGFR3

    FGFR3, IC50:150 nM

  • FGFR4

    FGFR4, IC50:3 nM
描述 The FGFR (fibroblast growth factor receptor) family, comprising four members FGFR1 - 4, plays critical roles in a variety of normal developmental and physiological processes. The FGF19-FGFR4 signaling axis has been implicated in the pathogenesis of several cancers, including hepatocellular carcinomas in mice and potentially in humans. BLU9931 is exquisitely selective for FGFR4, with IC50 value of 3 nM for FGFR4, versus other FGFR family members (IC50 = 150 nM for FGFR3) and all other kinases. Treatment with BLU9931 demonstrated selective, potent and dose-dependent reduction of phosphorylation of FGFR4 signaling pathway components, including FRS2, MAPK and AKT, with complete inhibition at concentration≥10 nM in MDA-MB-453 cells . BLU9931 showed anti-proliferative effect on HCC cell lines expressing an intact FGFR4 signaling complex with EC50 values < 1 μM. BLU9931 exhibited durable pathway inhibition in Hep3B cells, as leading to decreased levels of pFRS2 and pMAPK brief exposure, as well as a prolonged effect of an increased expression of CYP7A1 mRNA, the more distal biomarker of FGF19/FGFR4 signaling, due to reversal of a negative feedback loop. Oral administration of BLU9931 twice daily for 21 days resulted in dose-dependent growth inhibition of tumors at dose of 10, 30 and 100 mg/kg in Hep 3B xenograft mice. Same with that, twice-daily treatment with BLU9931 at dose of 10 - 300 mg/kg led to tumor regression in the FGF19-overexpressing PDX-derived xenograft LIXC012[1].
作用机制 BLU9931 can form a covalent bond with Cys552 in the ATP-binding pocket of FGFR4[1].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.96mL

0.39mL

0.20mL

9.82mL

1.96mL

0.98mL

19.63mL

3.93mL

1.96mL
参考文献

[1]Hagel M, Miduturu C, et al. First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway. Cancer Discov. 2015 Apr;5(4):424-37.