| Identification | Back Directory | [Name]
2-Propenamide, N-[(3R,4S)-4-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-7,8-dihydro-8-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]tetrahydro-3-furanyl]- | [CAS]
1628793-01-0 | [Synonyms]
FGFR4-IN-5
2-Propenamide, N-[(3R,4S)-4-[[6-(2,6-dichloro-3,5-dimethoxyphenyl)-7,8-dihydro-8-methyl-7-oxopyrido[2,3-d]pyrimidin-2-yl]amino]tetrahydro-3-furanyl]- | [Molecular Formula]
C23H23Cl2N5O5 | [MDL Number]
MFCD34470864 | [MOL File]
1628793-01-0.mol | [Molecular Weight]
520.37 |
| Chemical Properties | Back Directory | [density ]
1.47±0.1 g/cm3(Predicted) | [storage temp. ]
Store at -20°C | [solubility ]
DMSO : 100 mg/mL (192.17 mM; Need ultrasonic) | [form ]
Solid | [pka]
13.65±0.40(Predicted) | [color ]
White to off-white |
| Hazard Information | Back Directory | [Uses]
FGFR4-IN-5 is a potent and selective covalent FGFR4 inhibitor with an IC50 of 6.5 nM. FGFR4-IN-5 exhibits strong anti-tumor activity in vivo and can be used for hepatocellular carcinoma research[1]. | [Biological Activity]
FGFR4-IN-5 is a potent and selective covalent FGFR4 inhibitor with an IC50 of 6.5 nM. FGFR4-IN-5 exhibits strong anti-tumor activity in vivo and can be used for hepatocellular carcinoma research[1].
FGFR4-IN-5 (oral gavage; 10 mg/kg; single dose) reveals a high Cmax, low clearance, the Cmax values are 423 ng/ml, 588 ng/ml, and 2820 ng/ml in mice, rat and cynamolgus monkey, respectively. And the oral bioavailability are 20, 12, and 27% in mouse, rat, and cyno, respectively[1].FGFR4-IN-5 (oral gavage; 100 mg/kg; twice daily; 28 days) exhibits strong antitumor activity in an orthotopic Hep3B HTX model[1].FGFR4-IN-5 (oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days) results in dose-dependent growth inhibition of resistant tumors. Tumor regression is observed at 30 and 100 mg/kg, with %δT/δC of 67% and 70%, respectively. However, treatment with sorafenib at 100 mg/kg once daily does not provide any benefit in vivo[1]. | [in vivo]
FGFR4-IN-5 (oral gavage; 10 mg/kg; single dose) reveals a high Cmax, low clearance, the Cmax values are 423 ng/ml, 588 ng/ml, and 2820 ng/ml in mice, rat and cynamolgus monkey, respectively. And the oral bioavailability are 20, 12, and 27% in mouse, rat, and cyno, respectively[1].FGFR4-IN-5 (oral gavage; 100 mg/kg; twice daily; 28 days) exhibits strong antitumor activity in an orthotopic Hep3B HTX model[1].FGFR4-IN-5 (oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days) results in dose-dependent growth inhibition of resistant tumors. Tumor regression is observed at 30 and 100 mg/kg, with %ΔT/ΔC of 67% and 70%, respectively. However, treatment with sorafenib at 100 mg/kg once daily does not provide any benefit in vivo[1]. | Animal Model: | Hep3B cell bearing mice model[1] | | Dosage: | 100 mg/kg | | Administration: | Oral gavage; 100 mg/kg; twice daily; 28 days | | Result: | Resulted in tumor regression and sustained growth inhibition. |
| Animal Model: | Sorafenib-resistant tumors established to mice bearing Huh7 tumors[1] | | Dosage: | 10, 30, and 100 mg/kg | | Administration: | Oral gavage; 10, 30, and 100 mg/kg; twice daily; 11 days | | Result: | Resulted in dose-dependent growth inhibition of resistant tumors. |
| [IC 50]
FGFR4: 6.5 nM (IC50); FGFR2: 505 nM (IC50) | [References]
[1]. Haibo Liu, et al. Discovery of Selective, Covalent FGFR4 Inhibitors with Antitumor Activity in Models of Hepatocellular Carcinoma. ACS Med Chem Lett. 2020 Mar 6;11(10):1899-1904. |
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