Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Inhibition of IκB Kinase β (IKKβ) and Anti-diabetic Effect of SA51

  • Bhattarai, Bharat Raj (Department of Chemistry, University of Connecticut) ;
  • Kafle, Bhooshan (Department of Science and Humanities, Purwanchal Campus, Institute of Engineering, Tribhuvan University) ;
  • Hwang, Ji-Sun (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Han, Inn-Oc (Department of Physiology and Biophysics, College of Medicine, Inha University) ;
  • Cho, Hyeongjin (Department of Chemistry, College of Natural Science, Inha University)
  • Received : 2013.05.07
  • Accepted : 2013.05.30
  • Published : 2013.08.20
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Abstract

SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of $I{\kappa}B$ kinase ${\beta}$ ($IKK{\beta}$). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of $I{\kappa}B{\alpha}$ in macrophages. The effects of SA51 in mice were compared with those of structurally related compounds, SA18 and SA32, which were previously reported as inhibitors of both enzymes - less potent against $IKK{\beta}$ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for $IKK{\beta}^{+/-}$ mice. In contrast, SA18 and SA32 showed anti-obesity effects without anti-diabetic effects. Collectively, the effects of SA51 could be due largely to the inhibition of $IKK{\beta}$, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.

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References

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