FGFR4-IN-24
FGFR4-IN-24 is a selective irreversible covalent FGFR4 inhibitor (IC50 = 1.2 nM). FGFR4-IN-24 shows much weaker activity against the other three FGFR family kinases (FGFR1-3). FGFR4-IN-24 inhibits the FGF19/FGFR4 signaling pathway, effectively suppressing the proliferation of the HuH-7 HCC cell line (GI50 = 17 nM). FGFR4-IN-24 exhibits significant antitumor activity in a HuH-7 mouse xenograft model. FGFR4-IN-24 can be used for the research of hepatocellular carcinoma.
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- CAS. Nr.: 3053546-73-6
- Formel: C27H22FN5O3
- Molecular Weight:483.49
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biologische Aktivität
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Chemical Information
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Help & FAQs
Biologische Aktivität
Beschreibung
IC50 & Target
[1]|
FGFR4 1.2 nM (IC50) |
In Vitro
FGFR4-IN-24 (Compound 10v) (3 nmol/L, 0-30 min) shows a time-dependent enhancement in apparent inhibitory activity with prolonged preincubation, consistent with its ability to covalently modify FGFR4[1].
FGFR4-IN-24 (kinact/KI = 4.8 × 105 M-1s-1) exhibits superior potency, mainly due to its tighter binding to FGFR4 kinase (KI = 0.62 nM) from a binding mode that boosts noncovalent affinity[1].
FGFR4-IN-24 (72 h) inhibits the proliferation of HuH-7 cell line (IC50 = 1.2 nM, GI50 = 17 nM)[1].
FGFR4-IN-24 (1 μM) exhibits substantial inhibition of FGFR4 (79%) with high selectivity[1].
FGFR4-IN-24 (1-1000 nM, 2 h) inhibits the phosphorylation of the FGFR4 substrate FRS2α and reduces the phosphorylation levels of ERK in HuH-7 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:HuH-7 cells
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Concentration:
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Incubation Time:72 h
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Result:Induced a growth inhibition 50% (GI50) of 17 nM.
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Cell Line:HuH-7 cells
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Concentration:1, 3, 10, 30, 100, 300, 1000 nM
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Incubation Time:2 h
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Result:Inhibited almost completely the phosphorylation of FRS2α at 100 nM.
Reduced the phosphorylation levels of ERK.
Maintained the inhibition of FRS2α and ERK phosphorylation at 300 nM even after extensive washing with phosphate-buffered saline (PBS) (HY-K3005).
Parmacokinetics
| Species | Dose | Route | T1/2 | MRT | Vz | Vss | CL | Cmax | AUC0-t | AUC0-∞ | Bioavailability | Tmax |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 2 mg/kg | i.v. | 0.5 h | 0.3 h | 0.37 L/kg | 0.15 L/kg | 8.28 mL/min/kg | 17449 ng/mL | 4143 ng·h/mL | 4147 ng·h/mL | / | / |
| Mice[1] | 5 mg/kg | i.p. | 12.7 h | 4.87 h | / | / | / | 2377 ng/mL | 10331 ng·h/mL | 12421 ng·h/mL | 120 % | 0.83 h |
| Mice[1] | 5 mg/kg | p.o. | 0.98 h | 0.74 h | / | / | / | 65.8 ng/mL | 55.2 ng·h/mL | 75.4 ng·h/mL | 0.73 % | 0.25 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:HuH-7 xenograft mouse model in female BALB/c nude mice (4 weeks)[1]
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Dosage:25, 50 mg/kg
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Administration:Intraperitoneal administration (i.p.), twice daily for 21 days
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Result:Significantly inhibited tumor growth at 25 mg/kg, with a tumor growth inhibition (TGI) ratio of 85%.
Caused tumor regression at 50 mg/kg, with a TGI ratio of 114%.
Induced no significant reduction in body weight.
Chemical Information
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CAS. Nr. 3053546-73-6
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Molecular Weight 483.49
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Formel C27H22FN5O3
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SMILES
C=CC(NC1=CC=CC=C1NC2=CC=C(C(C(C3=C(F)C=CC(C(NC4CC4)=O)=C3)=O)=CN5)C5=N2)=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
FGFR4-IN-24 Related Classifications
HY-179381 Related Classifications
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