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].
IM-12 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
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
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