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].
LY2090314 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
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