FGF-401

Research use only, not for human use.

FGF-401 (NVP-FGF401, Roblitinib, FGF401) is a first-in-class, potent, highly selective FGFR4 inhibitor with IC50 of 1.1 nM.

FGF-401 (NVP-FGF401, Roblitinib, FGF401) is a first-in-class, potent, highly selective FGFR4 inhibitor with IC50 of 1.1 nM; shows >1,000-fold selectivity against of panel of 65 kinases and in a kinome of 456 kinases; potently inhibits phospho-FGFR4 in vivo, exhibits anti-tumor activity in s several xenograft animal models.Liver Cancer Phase 2 Clinical(In Vitro):Roblitinib (FGF-401; Compound Example 83) is a highly selective and potent FGFR4 inhibitor (IC50= 1.9 nM).Roblitinib shows no activity FGFR1, FGFR2, FGFR3, rat FGFR4, C552A FGFR4 (all IC50>10 uM).Roblitinib inhibits HUH7 (IC50=12 nM), Hep3B (IC50=9 nM), JHH7 (IC50=9 nM), HEPG2 (IC50>10 uM), JHH (IC50>10 uM).(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.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.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) .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.

Roblitinib (FGF-401; Compound Example 83) is a highly selective and potent FGFR4 inhibitor (IC50= 1.9 nM). Roblitinib shows no activity FGFR1, FGFR2, FGFR3, rat FGFR4, C552A FGFR4 (all IC50>10 uM). Roblitinib inhibits HUH7 (IC50=12 nM), Hep3B (IC50=9 nM), JHH7 (IC50=9 nM), HEPG2 (IC50>10 uM), JHH (IC50>10 uM).

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. 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.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) . 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. Animal Model:Male Wistar Hannover rats (Hep3B xenograft model) 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)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.

NVP-FGF401 | Roblitinib | FGF401

Angiogenesis

FGFR

FGFR4

Cancer

Liver Cancer

1708971-55-4

506.567

C25H30N8O4

>98% (HPLC)

DMSO: 6 mg/mL (Need Ultrasonic)

CN1CC(N(CC2=CC(CCCN3C(NC4=CC(NCCOC)=C(C#N)C=N4)=O)=C3N=C2C=O)CC1)=O

1,8-Naphthyridine-1(2H)-carboxamide, N-[5-cyano-4-[(2-methoxyethyl)amino]-2-pyridinyl]-7-formyl-3,4-dihydro-6-[(4-methyl-2-oxo-1-piperazinyl)methyl]-

(-20℃)

With Ice Pack

≥ 2 years