5.38776

FGFR4 Inhibitor, BLU9931

• Synonym(e): FGFR4 Inhibitor, BLU9931, Fibroblast Growth Factor Receptor 4 Inhibitor, BLU9931
• Empirische Formel (Hill-System): C₂₆H₂₂Cl₂N₄O₃
• Molekulargewicht: 509.38
• UNSPSC-Code: 12352200
• NACRES: NA.77

Eigenschaften

• Assay: ≥98% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Wirksamkeit: 3 nM IC₅₀
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: off-white
• Löslichkeit: DMSO: 100 mg/mL
• Lagertemp.: −20°C

Beschreibung

Allgemeine Beschreibung

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. Wirkung

Cell permeable: yes

Primary Target
FGFR4

Reversible: no

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.

Sonstige Hinweise

Hagel, M., et al. 2015. Cancer Discov.5, 424.

Rechtliche Hinweise

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable