1. Design, synthesis and insulin-sensitising effects of novel PTP1B inhibitors
- Author
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Tang, Yan-Bo, Lu, Dianyun, Chen, Zheng, Hu, Chun, Yang, Ying, Tian, Jin-Ying, Ye, Fei, Wu, Li, Zhang, Zhong-Yin, and Xiao, Zhiyan
- Subjects
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INSULIN resistance , *SULFATHIAZOLES , *LABORATORY mice , *ALLOSTERIC proteins , *RECOMBINANT proteins - Abstract
Abstract: Fifteen novel sulfathiazole-related compounds were designed as PTP1B inhibitors based on a previously reported allosteric inhibitor (1) of PTP1B. These compounds were synthesized and evaluated against human recombinant PTP1B. Six compounds (3, 4, 8 and 14–16) exhibited significant inhibitory activity against PTP1B. The most active compound (16) showed IC50 value of 3.2μM and kinetic analysis indicated that it is a non-competitive inhibitor of PTP1B. Furthermore, compound 16 demonstrated excellent selectivity to PTP1B over other PTPs. It also displayed in vivo insulin sensitizing effect in the insulin resistant mice. [Copyright &y& Elsevier]
- Published
- 2013
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