Alofanib (RPT835) is a potent and selective allosteric inhibitor of fibroblast growth factor receptor 2 (FGFR2). Anticancer and antiangiogenic activity.
IC50&Target
FGFR2
体外研究
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).
体内研究
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.
分子式
C19H15N3O6S
分子量
413.40
CAS号
1612888-66-0
运输条件
Room temperature in continental US; may vary elsewhere.