Alofanib

SKU: orb1221204

Description

Alofanib is a selective allosteric inhibitor of FGFR2 and has a dramatic inhibitory effect on FGF2-induced phosphorylation of FRS2a in KATO III cells (IC50 <10 nM). It has no direct effect on FGF2-dependent FGFR1 and FGFR3 phosphorylation levels in either cell lines and no effects on FGF2-FGFR2 binding.(In Vitro):Alofanib inhibits phosphorylation of FRS2α with IC50s of 7 and 9 nM in hFOB and SUM 52PE cells expressing different FGFR2 isoforms.Alofanib (0.2-0.8 μM, 6 hours) inhibits FGF-mediated proliferation in a panel of four cell lines representing several tumour types (triple-negative breast cancer, melanoma, and ovarian cancer) with GI50s of 16-370 nM.(In Vivo):In a FGFR-driven human tumour xenograft model, oral administration of alofanib (30 mg/kg, gavage, daily, 40 days, N=10) is well tolerated and results in potent antitumour activity.Treatment with alofanib (10 mg/kg/d, 0, 3 and 6 d, intraperitoneally) ablates experimental FGF-induced angiogenesis in vivo.

Key Properties

• CAS Number: 1612888-66-0
• MW: 413.4
• Purity: >98% (HPLC)
• Formula: C₁₉H₁₅N₃O₆S
• SMILES: Cc1cc(c(NS(=O)(=O)c2cccc(c2)C(O)=O)cc1-c1cccnc1)[N+]([O-])=O
• Target: FGFR
• Solubility: DMSO: 50 mg/mL;Water: Insoluble

Bioactivity

• In Vivo:
  In a FGFR-driven human tumour xenograft model, oral administration of alofanib (30 mg/kg, gavage, daily, 40 days, N = 10) is well tolerated and results in potent antitumour activity. Treatment with alofanib (10 mg/kg/d, 0, 3 and 6 d, intraperitoneally) ablates experimental FGF-induced angiogenesis In vivo. Animal model: C57Bl/6 × DBA/2 F1 mice of 22–30 g. Dosage: 10 mg/kg/d. Administration: Intraperitoneally, 0, 3 and 6 d. Result: Alofanib inhibits angiogenesis in mouse models.
• In Vitro:
  Alofanib inhibits phosphorylation of FRS2α with IC50s of 7 and 9 nM in hFOB and SUM 52PE cells expressing different FGFR2 isoforms. Alofanib (0.2-0.8 μM, 6 hours) inhibits FGF-mediated proliferation in a panel of four cell lines representing several tumour types (triple-negative breast cancer, melanoma, and ovarian cancer) with GI50s of 16-370 nM. Cell Proliferation Assay Cell line: SKOV3, HS478T, Mel Kor cells. Concentration: 0.2, 0.4, 0.8 μM Incubation time: 6 hours after dosing, FGF2 is added at a concentration of 25 ng/ml. Result: Inhibited growth of SKOV3 and HS578T cells with GI50s of 0.37 and 0.21 μM. Did not potently inhibit growth of Mel Kor cells that do not contain FGFR2 (GI50>10 μM).

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

RPT835

Quick Database Links

Gene Symbol

FGFR