FGFR4 INHIBITOR BLU9931 1PC X 10MG (C15-1305-355)

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; k_inact/K_I = 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 t_1/2 = 2.3 h (~ 10 mg/kg, p.o.).

Biochem/physiol Actions

Cell permeable: yes

Primary Target
FGFR4

Reversible: no

Packaging

Packaged under inert gas

Warning

Toxicity: Standard Handling (A)

Reconstitution

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

Molecular Weight: 509.38. Empirical Formula: C₂₆H₂₂Cl₂N₄O₃. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. potency: 3 . nM IC₅₀. manufacturer/tradename: Calbiochem^®. . storage condition: OK to freeze, protect from light. color: off-white. solubility: DMSO: 100 . mg/mL. storage temp.: −. 20°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.