Alofanib

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

Alofanib 是 FGFR2 的选择性变构抑制剂，对 KATO III 细胞中 FGF2 诱导的 FRS2a 磷酸化具有显着的抑制作用 (IC50 <10 nM)。

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.

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).

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.

RPT835

Angiogenesis

FGFR

FGFR2

Cancer

Ovarian Cancer

1612888-66-0

413.4

C19H15N3O6S

>98% (HPLC)

DMSO: 50 mg/mL;Water: Insoluble

Cc1cc(c(NS(=O)(=O)c2cccc(c2)C(O)=O)cc1-c1cccnc1)[N+]([O-])=O

3-(N-(4-methyl-2-nitro-5-(pyridin-3-yl)phenyl)sulfamoyl)benzoic acid

(-20℃)

With Ice Pack

≥ 2 years