3-[(3-氯-4-羟苯基)氨基]-4-(2-硝苯基)-1H-吡咯-2,5-二酮-abs812048

一、产品概述

二、产品信息

SB 415286 inhibits GSK3α in an ATP competitive manner with Ki of 31 nM and shows similar potency against GSK3β. SB 415286 has little or no activity against 24 other protein kinases with IC50 > 10 μ M. SB 415286 stimulates glycogen synthesis in the Chang human liver cell line with EC50 of 2.9 μM, and induces expression of a β-catenin-LEF/TCF regulated reporter gene in HEK293 cells. SB 415286 protects both central and peripheral nervous system neurones in culture from death induced by reduced PI3-kinase pathway activity in a concentration-dependent manner, which is correlated with inhibition of GSK-3 activity and modulation of GSK-3 substrates tau and β-catenin. In L6 myotubes, SB 415286 induces a much greater activation of GS (6.8-fold) compared to that elicited by insulin (4.2-fold) or Li (4-fold). SB 415286 (10 μM) inhibits rapamycin-induced down-regulation of cyclin D1, and blocks rapamycin and paclitaxel-induced apoptosis, suggesting a critical role for GSK3β in rapamycin-mediated paclitaxel-sensitization. SB 415286 prevents coxsackievirus-induced cell death in a dose-dependent manner via stabilization of β-catenin. SB 415286 exerts a protective effect on hydrogen peroxide-induced cell death in B65 rat neuroblastoma cells and neurons, while lithium does not attenuate the toxic effects of hydrogen peroxide. SB 415286 treatment potentiates TRAIL- and CH-11-induced apoptosis in HepG2 cells. Inhibition of GSK-3 by SB 415286 causes multiple myeloma (MM) cell growth arrest and apoptosis through the activation of the intrinsic pathway. SB 415286 decreases the viability of Neuro-2A cells, and induces the accumulation of cells in the G2/M phase of the cell cycle and subsequent apoptosis.

Administration of SB 415286 (~10 mg/kg twice daily) reduces the extent and degree of the trinitrobenzene sulphonic acid (TNBS)-provoked colonic inflammation in the rat, and reduces the fall in body weight, which is related to downregulation of NF-κB activity, involved in the generation of proinflammatory mediators. SB 415286 treatment at 1 mg/kg significantly delays the growth of Neuro-2A cells in vivo in nude mice.

三、背景

四、制备和贮存

五、产品特点

六、注意事项