FGFR4-IN-5, a covalent FGFR4 inhibitor, demonstrates potency and selectivity with an IC50 value of 6.5 nM. Exhibiting significant in vivo anti-tumor activity, it is applicable for research in hepatocellular carcinoma [1].

FGFR4:6.5 nM (IC50), FGFR2:505 nM (IC50)

FGFR4-IN-5, administered via oral gavage at 10 mg/kg (single dose), shows high Cmax and low clearance, with Cmax values of 423 ng/ml in mice, 588 ng/ml in rats, and 2820 ng/ml in cynomolgus monkeys, and oral bioavailability of 20%, 12%, and 27%, respectively [1]. FGFR4-IN-5 (oral gavage; 100 mg/kg; twice daily; 28 days) demonstrates significant antitumor activity in an orthotopic Hep3B HTX model [1]. FGFR4-IN-5 (oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days) induces dose-dependent tumor growth inhibition, with regression at 30 and 100 mg/kg and %δT/δC values of 67% and 70%, respectively, while sorafenib (100 mg/kg; once daily) shows no in vivo benefit [1].