Disease relevance of Lopac-S-3442

• Rats were treated with vehicle, morphine (300 microg/kg), the delta-opioid agonist fentanyl isothiocynate (FIT, 10 microg/kg), or the GSK inhibitor SB-216763 (SB21, 600 microg/kg) 10 min before ischemia [1].

High impact information on Lopac-S-3442

• We show that three different GSK-3 antagonists (LiCl, SB-216763, and SB-415286) can inhibit the growth cone collapse response induced by Sema 3A [2].
• Second, a pharmacological inhibitor of glycogen synthase kinase-3 beta, SB-216763, activated beta-catenin-mediated transcription, and enhanced the survival of CLL lymphocytes [3].
• The transcriptional induction of COX-2 and IL-8 by GSK-3 inhibition was further demonstrated by the increased COX-2 and IL-8 promoter activity after SB-216763 treatment or transfection with GSK-3alpha or GSK-3beta siRNA [4].
• Thus, SB-216763 and SB-415286 stimulated glycogen synthesis in human liver cells and induced expression of a beta-catenin-LEF/TCF regulated reporter gene in HEK293 cells [5].
• We show that the novel potent and selective small-molecule inhibitors of GSK-3; SB-415286 and SB-216763, protect both central and peripheral nervous system neurones in culture from death induced by reduced PI 3-kinase pathway activity [6].

Biological context of Lopac-S-3442

• However, the selective glycogen synthase kinase-3beta inhibitors SB-415286 and SB-216763 were unable to prevent colchicine-induced apoptosis in these cells, suggesting that the anti-apoptotic activity of lithium is not mediated by glycogen synthase kinase-3beta under these conditions [7].

Gene context of Lopac-S-3442

• To mimic phosphorylation-induced inhibition of GSK-3 beta activity, SB-216763 (SB), a GSK-3 beta inhibitor, was administered before ischemia or 5 min before reperfusion [8].
• By comparison, treatment with SB-216763 and SB-415286 proved more potent in terms of neuroprotection, and correlated with inhibition of GSK-3 activity towards GS in addition to Tau and beta-catenin [9].

References