FGF-401

SKU: orb1225952

Description

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.

Research Area

Stem Cell & Developmental Biology

Key Properties

• CAS Number: 1708971-55-4
• MW: 506.567
• Purity: >98% (HPLC)
• Formula: C₂₅H₃₀N₈O₄
• SMILES: CN1CC(N(CC2=CC(CCCN3C(NC4=CC(NCCOC)=C(C#N)C=N4)=O)=C3N=C2C=O)CC1)=O
• Target: FGFR
• Solubility: DMSO: 6 mg/mL (Need Ultrasonic)

Bioactivity

• 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. 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.
• 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).

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

NVP-FGF401 | Roblitinib | FGF401

Quick Database Links

Gene Symbol

FGFR