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Bulletin of the Korean Chemical Society (BKCS)

ISSN 0253-2964(Print)
ISSN 1229-5949(Online)
Volume 34, Number 8
BKCSDE 34(8)
August 20, 2013

Title	Inhibition of IκB Kinase β (IKKβ) and Anti-diabetic Effect of SA51
Author	Bharat Raj Bhattarai, Bhooshan Kafle, Ji-Sun Hwang, Inn-Oc Han, Hyeongjin Cho
Keywords	IKKβ Inhibitor, Hypoglycemic agent, PTP1B
Abstract	SA51, a medium potency inhibitor of protein tyrosine phosphatase 1B (PTP1B), was identified to be a potent inhibitor of IκB kinase β (IKKβ). Consistent with this, SA51 prevented lipopolysaccharide (LPS)-induced breakdown of IκBα 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 IKKβ but more potent against PTP1B compared to SA51. SA51 improved glucose tolerance and lipid parameters in mice, consistent with the results reported for IKKβ+/− 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 IKKβ, whereas SA18 and SA32 may be more likely to inhibit PTP1B, consistent with their relative in vitro inhibitory effects.
Page	2487 - 2490
Full Text	PDF

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