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LY2874455

现货
Catalog No.
A3576
FGF/FGFR抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 2,000.00
现货
5mg
¥ 1,380.00
现货
25mg
¥ 4,180.00
现货
100mg
¥ 6,980.00
现货

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Background

LY2874455 is a novel and potent FGFR inhibitor with IC50 value of 7 nM [1].

Fibroblast growth factor receptors (FGFRs) are receptors bind ligand of FGF family, which have a intracellular domain with tyrosine kinase activity. The binding of FGF triggers receptor dimerization and thus the activation of tyrosine kinase activity. Activated tyrosine kinase phosphorylates various downstream factors to induce downstream signaling, including FGF substrate 2 (FGS2). This signaling pathway contributes to FGFR-mediated cell proliferation and migration, which are involved in tumor formation and progression.

In HUVECs cell line expressing FGFR1 and RT-112 cell line expressing FGFR3, LY2874455 treatment resulted in inhibition of FGF2 and FGF9 induced Erk phosphorylation, which indicated the inhibitory activity of LY2874455 for FGFR1 and FGFR3 [1]. In SNU-16 and KATO-Ш cell line, the inhibition of FGFR2 phosphorylation was also observed, which indicated a direct inhibition by LY2874455 [2]. Additionally, when several multiple myeloma cancer cell lines were treated with LYS2874455, the cell lines with chromosomal translocation that resulted in overexpression of FGFR3 were significantly more susceptible to the inhibition of LY2874455 [2]. It suggested FGFR was the specific target of LY2874455 inhibition.

In RT-112, SNU-16, OPM-2 and NCI-H460 xenograft tumor model, treatment of LY2874455 twice a day (1.5 mg/kg and 3 mg/kg) resulted in significant dose-dependent reduction of cellular level of phosphorylated FGFR, and also regression of tumor growth. It indicated the inhibitory activity of LY2874455 in vivo [2].

Reference:
[1] Zhao, G S 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. Molecular Cancer Therapeutics. 2011, 10(11): 2200-2210.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt444.31
Cas No.1254473-64-7
FormulaC21H19Cl2N5O2
SynonymsLY 2874455; LY-2874455
Solubility≥44.4 mg/mL in DMSO, ≥6.34 mg/mL in EtOH with ultrasonic and warming, <2.56 mg/mL in H2O
Chemical Name2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol
SDFDownload SDF
Canonical SMILESCC(C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3C=CC4=CN(N=C4)CCO
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验 [1]:

细胞系

HUVECs和RT-112细胞,胃癌细胞系SNU-16和KATO-III

溶解方法

该化合物在DMSO中的溶解度大于22.2 mg/mL。若获取更高浓度的溶液,可在37℃下孵育10分钟,随后在超声波浴中摇匀。-20℃以下可储存数月。

反应条件

37°C,1小时

应用

LY2874455以剂量依赖性方式有效抑制HUVECs和RT-112两种细胞系中FGF2和FGF9诱导的Erk磷酸化,IC50值为0.3-0.8 nmol/L。LY2874455抑制SNU-16和KATO-III细胞中的FGFR2磷酸化,IC50值分别为0.8和1.5 nmol/L。 LY2874455抑制FRS2的磷酸化,FRS2是这些细胞系中FGFR的即时下游靶点,IC50值为0.8-1.5 nmol/L。

动物实验 [1]:

动物模型

FGFR或FGF表达水平改变的癌细胞系异种移植小鼠,包括过表达FGFR3的RT-112、FGFR2扩增的SNU-16、过表达突变型FGFR3的OPM-2和表达高水平FGF2的NCI-H460

给药剂量

1 mg/kg,3 mg/kg,每天

应用

在测试的4种肿瘤模型中,LY2874455以剂量依赖性方式快速稳定的抑制肿瘤生长。LY2874455引起RT-112、SNU-16和OPM-2肿瘤模型中肿瘤生长的显著消退,特别是当以3mg/kg每日两次给药。

注意事项

由于实验环境的不同,实际溶解度可能与理论值略有不同,请测试室内所有化合物的溶解度。

References:

[1]. Zhao G, Li W, Chen D, 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[J]. Molecular cancer therapeutics, 2011, 10(11): 2200-2210.

生物活性

Description LY2874455是一种有效的成纤维细胞生长因子受体(FGFR)选择性小分子抑制剂,对FGFR1、2、3和4的IC50值分别为2.8、2.6、6.4和6 nM。
靶点 FGFR1 FGFR2 FGFR3 FGFR4    
IC50 2.8 nM 2.6 nM 6.4 nM 6 nM    

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