Merck, 5387760001, FGFR4 Inhibitor, BLU9931

General description
A cell-permeable anilinoquinazoline derivative that acts as a highly potent, irreversible, paralog selective inhibitor of fibroblast growth factor receptor 4 kinase (FGFR4; IC₅₀ = 3 nM; kinact/KI = 0.6 x 10⁵ (mol/L) ⁻¹s⁻¹). Acts by forming a covalent bond with Cys552 within the ATP-binding pocket of FGFR4. Has minimal effect on FGFR1, 2, and 3 (IC₅₀ = 591 nM, 493 nM, and 150 nM respectively) and does not display any activity towards a panel of 455 other protein kinases. Suppresses FGFR4 signaling and phosphorylation of downstream components in MDA-MB-453 cells. Also shown to be a potent inhibitor of downstream signaling in Hep 3B hepatocellular carcinoma (HCC) cells expressing FGF19 and induces caspase 3 and 7 activity. Inhibits the growth of Hep 3B HCC xenografts in murine model (100 mg/kg, b.i.d; p.o. for 21 days). Displays desirable pharmacokinetic properties with moderate bioavailability (18%) and t₁/₂ = 2.3 h (~ 10 mg/kg, p.o.).
Biochem/physiol Actions
Cell permeable: yes
Primary Target
FGFR4
Reversible: no
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Hagel, M., et al. 2015. Cancer Discov.5, 424.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)