FGF-401
FGF-401 Basic information
- Product Name:
- FGF-401
- Synonyms:
-
- N-(5-cyano-4-((2-methoxyethyl)amino)pyridin-2-yl)-7-formyl-6-((4-methyl-2-oxopiperazin-1-yl)methyl)-3,4-dihydro-1,8-naphthyridine-1(2H)-carboxamide
- N-[5-cyano-4-(2-methoxyethylamino)pyridin-2-yl]-7-formyl-6-[(4-methyl-2-oxopiperazin-1-yl)methyl]-3,4-dihydro-2~{H}-1,8-naphthyridine-1-carboxamide
- Roblitinib（FGF-401）
- FGF 401;FGF-401
- 8-naphthyridine-1(2H)-carboxamide
- 0997
- N-[5-Cyano-4-[(2-methoxyethyl)amino]-2-pyridinyl]-7-formyl-3,4-dihydro-6-[(4-methyl-2-oxo-1-piperazinyl)methyl]-1,8-naphthyridine-1(2H)-carboxamide
- Roblitinib
- CAS:
- 1708971-55-4
- MF:
- C25H30N8O4
- MW:
- 506.56
- Product Categories:
-
- API
- Mol File:
- 1708971-55-4.mol
FGF-401 Chemical Properties
- Boiling point:
- 852.1±65.0 °C(Predicted)
- Density
- 1.39±0.1 g/cm3(Predicted)
- storage temp.
- Store at -20°C
- solubility
- DMSO:5.4(Max Conc. mg/mL);10.66(Max Conc. mM)
Chloroform:30.0(Max Conc. mg/mL);59.22(Max Conc. mM) - form
- A crystalline solid
- pka
- 11.40±0.20(Predicted)
- color
- White to off-white
- InChIKey
- BHKDKKZMPODMIQ-UHFFFAOYSA-N
- SMILES
- N1(C(NC2=NC=C(C#N)C(NCCOC)=C2)=O)C2C(=CC(CN3CCN(C)CC3=O)=C(C=O)N=2)CCC1
FGF-401 Usage And Synthesis
Description
FGF401 is an inhibitor of FGF receptor 4 (FGFR4; IC50 = 1.9 nM). It inhibits proliferation of Huh7 carcinoma cells with an IC50 value of 12 nM. FGF401 induces bile acid synthesis in dogs, increasing plasma and fecal levels of bile acids when administered at a dose of 45 mg/kg per day for four weeks. It also decreases serum cholesterol when administered at doses ranging from 5 to 45 mg/kg per day.
Uses
Roblitinib (FGF-401) is an orally active and highly selective FGFR4 inhibitor with an IC50 of 1.9 nM[1]. Roblitinib has antitumor activity[2].
in vivo
Roblitinib (gavage; 10-100 mg/kg; b.i.d.; for 10 days) with the 30 mg/kg has the maximal level of inhibition of FGFR4-dependent tumor growth in the Hep3B xenograft model[1].
Roblitinib causes blood concentrations dropped below the IC90 threshold level within 8 h of dosing, and controlles tumor growth to the level of stasis at the lowest dose of 10 mg/kg for 6 days[1].
Roblitinib (iv at 1 mg/kg; po at 3 mg/kg) has a T1/2 of 1.4 hours, a CL of 28 mL/min kg, and a Vss of 2.3 L/kg for Male mice (C57BL/6) [1].
Roblitinib (iv at 0.5 mg/kg; po at 3 mg/kg) has a T1/2 of 4.4 hours, a CL of 19 mL/min kg, and a Vss of 3.9 L/kg for male SD rats[1].
| Animal Model: | Male Wistar Hannover rats (Hep3B xenograft model)[1] |
| Dosage: | 10, 30, 100 mg/kg |
| Administration: | Gavage; for 10 days |
| Result: | Caused blood concentrations dropped below the IC90 threshold between 8 and 12 h following dosing. Had the maximal level of inhibition of FGFR4-dependent tumor growth in the Hep3B xenograft model. |
| Animal Model: | Male mice (C57BL/6)[1] |
| Dosage: | 1 mg/kg or 3 mg/kg (Pharmacokinetic Analysis) |
| Administration: | IV at 1 mg/kg; PO at 3 mg/kg |
| Result: | Had a T1/2 of 1.4 hours, a CL of 28 mL/min?kg, and a Vss of 2.3 L/kg. |
IC 50
FGFR4: 1.9 nM (IC50); FGFR1: >10 μM (IC50); FGFR2: >10 μM (IC50); FGFR3: >10 μM (IC50); rat FGFR4: >10 μM (IC50)
References
[1] Nicole Buschmann, et al. Ring-fused bicyclic pyridyl derivatives as fgfr4 inhibitors. WO2015059668A1.
[2] Robin A Fairhurst, et al. Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4. J Med Chem. 2020 Nov 12;63(21):12542-12573. DOI:10.1021/acs.jmedchem.0c01019
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