LY2874455
(Synonyms: LY 2874455; LY-2874455) 目录号 : GC13424
A pan-FGFR inhibitor
Cas No.:1254473-64-7
Sample solution is provided at 25 µL, 10mM.
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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.
| Cell experiment [1]: | |
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Cell lines |
HUVECs and RT-112 cells, gastric cancer cell lines, SNU-16 and KATO-III |
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Preparation method |
The solubility of this compound in DMSO is >22.2mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
37°C, 1 hour |
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Applications |
LY2874455 potently inhibited the Erk phosphorylation induced by FGF2 and FGF9 in both HUVECs and RT-112 cell lines in a dose-dependent manner, with the IC50 values of 0.3 to 0.8 nmol/L. LY2874455 inhibited FGFR2 phosphorylation in SNU-16 and KATO-III cells, with estimated IC50 values of 0.8 and 1.5 nmol/L, respectively. LY2874455 inhibited the phosphorylation of FRS2, an immediate downstream target of FGFR in these cell lines, again with a similar potency of 0.8 to 1.5 nmol/L. |
| Animal experiment [1]: | |
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Animal models |
Mice xenografted with cancer cell lines with altered FGFR or FGF levels, RT-112 (overexpressing FGFR3), SNU-16 (amplified FGFR2), OPM-2 (overexpressing a mutant FGFR3), and NCI-H460 (a high level of FGF2) |
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Dosage form |
1 mg/kg, 3 mg/kg, every day |
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Application |
LY2874455 exhibited a rapid, robust, dose-dependent inhibition of tumor growth in all 4 models tested. LY2874455 caused a significant regression of tumor growth in the RT-112, SNU-16, and OPM-2 tumor models, especially when dosed at 3 mg/kg twice a daily. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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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. | |
| Cas No. | 1254473-64-7 | SDF | |
| 别名 | LY 2874455; LY-2874455 | ||
| 化学名 | 2-[4-[(E)-2-[5-[(1R)-1-(3,5-dichloropyridin-4-yl)ethoxy]-1H-indazol-3-yl]ethenyl]pyrazol-1-yl]ethanol | ||
| Canonical SMILES | CC(C1=C(C=NC=C1Cl)Cl)OC2=CC3=C(C=C2)NN=C3C=CC4=CN(N=C4)CCO | ||
| 分子式 | C21H19Cl2N5O2 | 分子量 | 444.31 |
| 溶解度 | ≥ 44.4 mg/mL in DMSO, ≥ 6.34 mg/mL in EtOH with ultrasonic and warming | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2507 mL | 11.2534 mL | 22.5068 mL |
| 5 mM | 0.4501 mL | 2.2507 mL | 4.5014 mL |
| 10 mM | 0.2251 mL | 1.1253 mL | 2.2507 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet