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Chemical Compound Review

Lopac-S-3567     3-[(3-chloro-4-hydroxy- phenyl)amino]-4-(2...

Synonyms: Tocris-1617, QCR-152, CHEMBL322970, SureCN454710, cc-259, ...
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Disease relevance of SB 415286

  • Administration of either TDZD-8 or SB 415286 reduced the fall in body weight following challenge with TNBS at each dose level studied [1].
  • The effects of the inhibitors of glycogen synthase kinase-3beta (GSK-3beta), TDZD-8 and SB 415286, which can substantially reduce the systemic inflammation associated with endotoxic shock in vivo, have now been investigated on the acute colitis provoked by trinitrobenzene sulphonic acid (TNBS) in the rat [1].

High impact information on SB 415286

  • However, exposure of undifferentiated myoblasts (day 3) to 50 microM SB-415286, a GSK3 inhibitor, led to a significant elevation in GS protein that was not accompanied by changes in the abundance of GLUT4, another late differentiation marker [2].
  • Only when muscle cells were incubated simultaneously with insulin and SB-415286 or with lithium (which stimulates GS and glucose transport) was an increase in glycogen accretion observed [2].
  • Treatment of cells with the GSK-3 inhibitors SB-415286 and LiCl(2) inhibited E-lam formation and prevented the accumulation of Rac1 and Arp2/3 complex at lamellipodia [3].
  • The increase in myeloperoxidase activity, an index of neutrophil infiltration into the TNBS-induced inflamed colon, was significantly inhibited by both TDZD-8 and SB 415286 at each dose level [1].
  • The elevated levels of the transcription factor NF-kappaB subunit p65, as determined by Western blot in the nuclear extracts from the TNBS-provoked inflamed colonic tissue, were dose-dependently reduced by TDZD-8 or SB 415286 treatment [1].

Biological context of SB 415286

  • Finally, we examined the pharmacological inhibitors of GSK3beta, GSK3 inhibitor I, TDZD-8, and SB-415286, for their ability to prevent low potassium (LK)-induced apoptosis [4].
  • SB-415286 on the other hand, was able to rescue CGNs from cell death [4].
  • The transient transfection of a constitutively active and non-phosphorylable S9AGSK-3beta mutant sensitized cells to etoposide cytotoxic effects while cell treatment with the small GSK-3beta inhibitor SB-415286 repressed the sensitizing effect of LY294002 on chemotherapy-induced apoptosis and caspase-8 activation [5].

Anatomical context of SB 415286

  • Whilst Li and SB-415286 both inhibit GSK3 in muscle and fat cells, only Li stimulated GT [6].
  • In L6 myotubes, SB-415286 induced a much greater activation of GS (6.8-fold) compared to that elicited by insulin (4.2-fold) or Li (4-fold) [6].

Gene context of SB 415286


  1. Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3beta. Whittle, B.J., Varga, C., Pósa, A., Molnár, A., Collin, M., Thiemermann, C. Br. J. Pharmacol. (2006) [Pubmed]
  2. Constitutive activation of GSK3 down-regulates glycogen synthase abundance and glycogen deposition in rat skeletal muscle cells. MacAulay, K., Blair, A.S., Hajduch, E., Terashima, T., Baba, O., Sutherland, C., Hundal, H.S. J. Biol. Chem. (2005) [Pubmed]
  3. Glycogen synthase kinase-3 regulates cytoskeleton and translocation of Rac1 in long cellular extensions of human keratinocytes. Koivisto, L., Häkkinen, L., Matsumoto, K., McCulloch, C.A., Yamada, K.M., Larjava, H. Exp. Cell Res. (2004) [Pubmed]
  4. Inhibition of GSK3beta is a common event in neuroprotection by different survival factors. Chin, P.C., Majdzadeh, N., D'Mello, S.R. Brain Res. Mol. Brain Res. (2005) [Pubmed]
  5. GSK-3beta reactivation with LY294002 sensitizes hepatoma cells to chemotherapy-induced apoptosis. Beurel, E., Kornprobst, M., Blivet-Van Eggelpoël, M.J., Cadoret, A., Capeau, J., Desbois-Mouthon, C. Int. J. Oncol. (2005) [Pubmed]
  6. Use of lithium and SB-415286 to explore the role of glycogen synthase kinase-3 in the regulation of glucose transport and glycogen synthase. MacAulay, K., Hajduch, E., Blair, A.S., Coghlan, M.P., Smith, S.A., Hundal, H.S. Eur. J. Biochem. (2003) [Pubmed]
  7. Lithium protects ethanol-induced neuronal apoptosis. Zhong, J., Yang, X., Yao, W., Lee, W. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
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