产品说明书

IM-12

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Chemical Structure| 1129669-05-1 同义名 : GSK3β Inhibitor XIX
CAS号 : 1129669-05-1
货号 : A235864
分子式 : C22H20FN3O2
纯度 : 98%
分子量 : 377.411
MDL号 : MFCD20527313
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 55 mg/mL(145.73 mM)，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：
生物活性
靶点

  • GSK-3β

    GSK-3β, IC50:53 nM
描述 GSK-3β is a serine/threonine kinase that plays a role in a broad range of activities in the cell. GSK-3β is an essential regulator in the WNT/ β-catenin pathway where it phosphorylates β-catenin committing it to degradation[3]. IM-12, a GSK-3β inhibitor, showed a bell-shaped dose-response relationship in a kinase activity assay of inhibition of GSK-3β, and itscalculated IC50 was 53 nM (luminescent kinase activity assay) [4]. Treatment of 3μM IM-12 had an ability to attenuate ReNcell VM cell’s proliferation (human neural progenitor cell line) in 72 h, increase nuclear accumulation of β-catenin in ST14A cells in 6h, upregulate TCF activity in ReNcell VM cells ( transfected with TOP/FOP plasmids or co-transfected with pCAGGS-S33Y) in 24h, and promote neuronal differentiation from ReNcell VM cells to f βIIItub+ cells in 3d , [4]. In a pig model of metabolic syndrome and chronic myocardial ischemia, treatment of IM-12(1.5mg/kg, daily) for 5 weeks improved vessel density in the ischemic and non-ischemic myocardial tissue, and increased myocardial blood flow both at rest and with pacing [5].
作用机制 IM-12 inhibits GSK-3β to activate Wnt-β catenin signaling pathway, which induces the decay of the degradation complex, stabilizing β catenin which then translocates into the nucleus where it binds to the T-cell factor (TCF)/lymphoid enhancer factor (LEF)-complex and regulates the transcription of Wnt-specific target genes [4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
ReNcell VM cells 3 uM Proliferation assay 72 h Antiproliferative activity against human ReNcell VM cells assessed as reduction of cell proliferation at 3 uM after 72 hrs 20708937
ST14A cells Function assay 6 h Inhibition of GSK-3-beta-mediated Wnt signaling in human ST14A cells assessed as increase in accumulation of beta-casein around nucleus after 6 hrs by microscopic analysis 20708937
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.65mL

0.53mL

0.26mL

13.25mL

2.65mL

1.32mL

26.50mL

5.30mL

2.65mL
参考文献

[1]Schmole AC, Brennfuhrer A, et al. Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells. Bioorg Med Chem. 2010 Sep 15;18(18):6785-95.

[2]Wang T, Duan YM, et al. IM-12 activates the Wnt-β-catenin signaling pathway and attenuates rtPA-induced hemorrhagic transformation in rats after acute ischemic stroke. Biochem Cell Biol. 2019 Dec;97(6):702-708.

[3] Ke B, Lu R, Zhang X. Phosphorylated Glycogen Synthase Kinase-3β (GSK-3β) Improves Cognition in Rats with Diabetes-Associated Cognitive Decline. Med Sci Monit. 2019 May 6;25:3336-3343. doi: 10.12659/MSM.914653. Retraction in: Med Sci Monit. 2019 Aug 21;25:6291. PMID: 31057171

[4] Schmöle AC. Novel indolylmaleimide acts as GSK-3beta inhibitor in human neural progenitor cells. Bioorg Med Chem. 2010 Sep 15;18(18):6785-95. doi: 10.1016/j.bmc.2010.07.045. Epub 2010 Jul 25.

[5] Potz BA. Calpain inhibition modulates glycogen synthase kinase 3β pathways in ischemic myocardium: A proteomic and mechanistic analysis. J Thorac Cardiovasc Surg. 2017 Feb;153(2):342-357. doi: 10.1016/j.jtcvs.2016.09.087. Epub 2016 Nov 16.