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LY2090314

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Chemical Structure| 603288-22-8 同义名 : -
CAS号 : 603288-22-8
货号 : A115111
分子式 : C28H25FN6O3
纯度 : 99%+
分子量 : 512.535
MDL号 : MFCD20526532
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(48.78 mM)，配合低频超声，并水浴加热至45℃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 40 mg/mL suspension

生物活性
靶点

  • GSK-3α

    GSK-3α, IC50:1.5 nM

  • GSK-3β

    GSK-3β, IC50:0.9 nM
描述 GSK-3 (Glycogen synthase kinase 3) is a serine/threonine protein kinase, consisting of GSK-3a and b subunit, which plays a key role in many different biological processes including tumorigenesis, cell survival and developmental patterning. GSK-3 is constitutively active in non-stimulated cells and can negatively regulate canonical Wnt/b-catenin signaling[1]. LY2090314 is a potent inhibitor of GSK-3 with IC50 values of 1.5 nM and 0.9 nM for GSK3a and GSKb (measured by enzyme activity of human recombinant GSK3), respectively. LY2090314 can activate the Wnt pathway in melanoma cell lines. Exposure of LY2090314 activated in a dose dependent manner in the TCF/LEF luminescent reporter in A375 cells following 5 hours. Treatment with 20 nM LY2090314 promoted a time-dependent stabilization of β-catenin total protein as well as an induction of Axin2, accompanied with inhibition of GSK3 phosphorylation at tyrosine 279 and β-catenin at serine 33/37 and threonine 41. LY2090314 (IC50 <0.05 μM) can potently induce apoptotic cell death in a range of melanoma cell lines and increase the level of activated caspase as well as cleaved PARP in A375, M14 and Mel1102 cells on dose of 15-40 nM[2]. Treatment with 15 - 30 μM LY2090314 led to dose-dependent enhancement of NK cell activity against an AML cell line, OCI-AML3 and primary AML patient samples[3].
作用机制 LY2090314 is a small molecule bisarylmaleimide, which is identified as potent ATP-competitive GSK-3 inhibitor[3].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human SY5Y cells Function assay Inhibition of Glycogen synthase kinase-3 beta dependent Tau protein serine-396 phosphorylation in human SY5Y cells, IC50=0.7 nM 15267232
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.95mL

0.39mL

0.20mL

9.76mL

1.95mL

0.98mL

19.51mL

3.90mL

1.95mL
参考文献

[1]Domoto T, Pyko IV, et al. Glycogen synthase kinase-3β is a pivotal mediator of cancer invasion and resistance to therapy. Cancer Sci. 2016 Oct;107(10):1363-1372.

[2]Atkinson JM, Rank KB, et al. Activating the Wnt/β-Catenin Pathway for the Treatment of Melanoma--Application of LY2090314, a Novel Selective Inhibitor of Glycogen Synthase Kinase-3. PLoS One. 2015 Apr 27;10(4):e0125028.

[3]Martinez A, Castro A, et al. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 2002 Jul;22(4):373-84.

[4]Zamek-Gliszczynski MJ, Abraham TL, et al. Pharmacokinetics, metabolism, and excretion of the glycogen synthase kinase-3 inhibitor LY2090314 in rats, dogs, and humans: a case study in rapid clearance by extensive metabolism with low circulating metabolite exposure. Drug Metab Dispos. 2013 Apr;41(4):714-26.