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LY2874455

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Chemical Structure| 1254473-64-7 同义名 : -
CAS号 : 1254473-64-7
货号 : A382878
分子式 : C21H19Cl2N5O2
纯度 : 99%+
分子量 : 444.314
MDL号 : MFCD22124884
存储条件：

粉末 Sealed in dry,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(112.53 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+2% Tween80+40% PEG300+water 6 mg/mL clear

PO 0.5% CMC-Na 30 mg/mL suspension

生物活性
靶点

  • VEGFR2

    VEGFR2, IC50:7 nM

  • FGFR2

    FGFR2, IC50:2.6 nM

  • FGFR3

    FGFR3, IC50:6.4 nM

  • FGFR4

    FGFR4, IC50:6 nM

  • FGFR1

    FGFR1, IC50:2.8 nM
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]
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.23mL

11.25mL

2.25mL

1.13mL

22.51mL

4.50mL

2.25mL
参考文献

[1]Zhao G, Li WY, et al. A novel, selective inhibitor of fibroblast growth factor receptors that shows a potent broad spectrum of antitumor activity in several tumor xenograft models. Mol Cancer Ther. 2011;10(11):2200-10.