BLU9931 是高度选择性的,不可逆的成纤维细胞生长因子受体 4 抑制剂,其IC50=3 nM,Kd=6 nM,具有抗肿瘤作用。
产品描述
BLU9931 is the first selective small molecule inhibitor of FGFR4.
体外活性
In MDA-MB-453 cells, BLU9931 potently inhibits phosphorylation of FGFR4 signaling pathway. BLU9931 inhibits 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 μM. BLU9931 also inhibits proliferation in PDX-derived cell lines with an intact FGFR4 signaling pathway. [1]
体内活性
In mice bearing the FGF19-amplified Hep 3B liver tumors, BLU9931 (300 mg/kg, p.o.) leads to tumor regression and prevents this weight loss induced by tumors. In mice bearing the FGF19-overexpressing PDX-derived LIXC012 xenografts, treatment with BLU9931 (300 mg/kg, p.o.) also leads to tumor regression. [1]
激酶实验
FGFR1-4 Biochemical Assays: FGFR kinase inhibition assays are performed at KM for ATP. Picomolar to low nanomolar concentrations of FGFR proteins are incubated in 1× Kinase Reaction Buffer (KRB) with 1 μM of CSKtide and 50 to 250 of μM ATP at 25°C for 90 minutes in the presence or absence of a dosed concentration series of inhibitor. All reactions are terminated by the addition of Stop buffer, and plates are read on a Caliper EZReader2. IC50 values are fit with a four-parameter log[Inhibitor] versus response model with floating Hill Slope.
细胞实验
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 viability is determined by CellTiter-Glo, and results represented as background-subtracted relative light units normalized to a DMSO-treated control. Relative EC50 values are determined at 50% inhibition between the top and bottom plateau of the dose–response curve.(Only for Reference)
Cas No.
1538604-68-0
分子式
C26H22Cl2N4O3
分子量
509.38
储存和溶解度
DMSO:10mM
Powder: -20°C for 3 years
In solvent: -80°C for 2 years