Design,synthesis and insulin-sensitising effects of novel PTP1B inhibitors |
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| Authors: | Yan-Bo Tang Dianyun Lu Zheng Chen Chun Hu Ying Yang Jin-Ying Tian Fei Ye Li Wu Zhong-Yin Zhang Zhiyan Xiao |
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| Institution: | 1. Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China;2. School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, PR China;3. Beijing Key Laboratory of New Drug Mechanisms and Pharmacological Evaluation Study, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China;4. Department of Biochemistry and Molecular Biology and Chemical Genomics Core Facility, Indiana University, School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA |
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| 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 3.2 μM 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. |
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