生物活性

• 靶点

  FGFR1 IC50:2.8nM

  FGFR2 IC50:2.6nM

  FGFR3 IC50:6.4nM

  FGFR4 IC50:6nM

  VEGFR2 IC50:7nM

• 描述The FGFR (fibroblast growth factor receptor) family, comprising four members, FGFR1, FGFR2, FGFR3 and FGFR4, belongs to the RTKs which serve as high affinity receptors for FGFs controlling cell proliferation, migration, apoptosis and differentiation. LY2874455 is a pan-FGFR inhibitor with IC50 values of 2.8nM, 2.6nM, 6.4nM and 6nM for FGFR1, 2, 3 and 4, respectively. LY2874455 inhibited p-FGFR2 with estimated IC50 values of 0.8nM and 1.5nM, respectively, in SNU-16 and KATO-III cells, as well as potently inhibit p-ERK induced by FGF2 and FGF9 in a dose-dependent manner, with average IC50 values of 0.3-0.8nM. LY2874455 showed more potent anti-proliferation in cells, such as SNU-16 and KATO-III with a highly amplified fgfr2, suggesting the direct link to the inhibition of FGFR signaling of its antiproliferative effect. LY2874455 exhibited an excellent pharmacokinetic/pharmacodynamic relationship as shown by its dose-dependent inhibition of the tumor growth at TED50 and TED90 (1 and 3 mg/kg, respectively), as well as a rapid, robust, dose-dependent inhibition of tumor growth in SNU-16, OPM-2, NCI-H460 and RT-112 xenograft models especially when dosed at 3 mg/kg twice a day^[1].
• 作用机制LY2874455 is an ATP-competitive type of molecule that inhibits FGFR activity via its occupation of the ATP-binding pocket of the enzyme.^[1]

• 动物研究
  剂量	Rat[2] (p.o.): 1 mg/kg - 10 mg/kg
  给药途径	p.o.