Inhibition of IKK-β: A new development in the mechanism of the anti-obesity effects of PTP1B inhibitors SA18 and SA32

Bharat Raj Bhattarai, Jeong Hyeon Ko, Suja Shrestha, Bhooshan Kafle, Heeyeong Cho, Ju Hee Kang, Hyeongjin Cho

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

In a previous study, protein tyrosine phosphatase 1B (PTP1B) inhibitors, SA18 and SA32, exhibited anti-obesity effects in a mouse model by suppressing weight gain and improving blood parameters, including free fatty acid (FFA) levels. In a separate study, depletion of the PTP1B gene in mice suppressed weight gain without significant change in FFA levels. The discrepancy in FFA concentrations between the two studies suggested that the in vivo target of the SA compounds might not be limited to PTP1B. In this study, SA18 and SA32 were found to be potent inhibitors of IκB Kinase-β (IKK-β). In vivo relevance of the inhibitory activity was evaluated in differentiated adipocytes. Inhibition of IKK-β, in addition to inhibition of PTP1B, in mice treated with the SA compounds, could be a possible mechanism of the compound's biological response including the resistance to diet-induced weight gain and improvement in blood parameters. As potent and cell-permeable IKK-β inhibitors, SA18 and SA32 could also be valuable in biological experiments.

Original languageEnglish
Pages (from-to)1075-1077
Number of pages3
JournalBioorganic and Medicinal Chemistry Letters
Volume20
Issue number3
DOIs
StatePublished - 1 Feb 2010
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by Inha University (2009). B.K. and B.R.B. were recipients of a BK21 fellowship.

Keywords

  • IKK-β
  • Inhibitor
  • Obesity
  • PTP1B

Fingerprint

Dive into the research topics of 'Inhibition of IKK-β: A new development in the mechanism of the anti-obesity effects of PTP1B inhibitors SA18 and SA32'. Together they form a unique fingerprint.

Cite this