Glycogen synthase kinase-3 (GSK-3) is a serine/threonine protein kinase encoded by two highly homologous and ubiquitously expressed genes with ability to phosphorylate and inactivate glycogen synthase, the rate limiting enzyme in glycogen synthesis. SB-415286 is a potent and selective inhibitor of GSK-3 with IC50s of 77.5 nM for both hGSK-3α and hGSK-3β and a Ki of 30.75 nM for hGSK-3α. In the Chang human liver cell line, SB-415286 stimulated glycogen synthase activity thus promoting glycogen synthesis with EC50 of 2.9 μM. Using a HEK293 transient transfection β-catenin-LEF/TCF luciferase reporter assay, SB-415286 dose-dependently induced transcription of the β-catenin dependent gene[3]. SB-415286 (25, 50 and 100 μM; 24, 48, 72 and 96 h) showed anti-proliferative effect in Neuro-2a, SK-N-SH and SK-N-BE cell lines in a dose and time dependent manner. In vivo, daily i.p. injections of SB-415286 produced a significant tumor growth delay in the tumor-bearing mice[4].
SB 415286 细胞实验
Cell Line
Concentration
Treated Time
Description
References
B65 neuroblastoma cells
5-44 µM
24 hours
To evaluate the antiproliferative effects of SB-415286 on B65 cells, results showed that SB-415286 significantly inhibited cell proliferation, causing G2/M arrest and inducing caspase-independent apoptosis.
J Cell Mol Med. 2009 Sep;13(9B):3906-17.
SB 415286 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
TNBS-induced acute colitis model
Subcutaneous injection
0.1, 0.33 or 1.0 mg/kg
Twice daily for 3 days
To evaluate the effects of SB 415286 on TNBS-induced colonic inflammation. The results showed that SB 415286 significantly reduced the extent and severity of colonic inflammation and inhibited the increase in MPO activity and TNF-α levels.
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