BLU9931

1538604-68-0

C26H22Cl2N4O3

DMSO : 17 mg/mL (33.37 mM; Need ultrasonic and warming); H2O : < 0.1 mg/mL (insoluble)

Protein Tyrosine Kinase/RTK

BLU9931 is a potent, selective, and irreversible FGFR4 inhibitor with IC₅₀ of 3 nM, about 297-, 184-, and 50-fold selectivity over FGFR1/2/3, respectively. IC50 & Target: IC50: 3 nM (FGFR4) In Vitro: 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 uM. BLU9931 also inhibits proliferation in PDX-derived cell lines with an intact FGFR4 signaling pathway^[1]. BLU9931 induces tumor shrinkage in hepatocellular carcinoma models that express a functioning ligand/receptor complex consisting of FGF19/FGFR4/KLB and adds to a growing list of anti-FGFR4 agents^[2]. In Vivo: BLU9931 (300 mg/kg, p.o.) leads to tumor regression and prevents this weight loss in mice bearing the FGF19-amplified Hep 3B liver 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].