Discovery of Bisindole as a Novel Scaffold for Protein Tyrosine Phosphatase 1B Inhibitors

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• 作者：Changcheng Jing ; Ziyan Li ; Kaili Jia ; Chen Chen ; Xiao Liu ; Beibei Wang ; Wenhao Hu ; Jia Li ; Tong Zhu and Suzhen Dong
• 刊名：Archiv der Pharmazie
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：350
• 期：1
• 全文大小：614K
• ISSN：1521-4184

文摘

Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an effective target for the treatment of both type II diabetes and obesity. However, no PTP1B inhibitor has come into clinic application. Herein, we report mixed 3,3′-bisindoles as novel PTP1B inhibitors with low micromole-ranged inhibitory activity. The best active compound 9f inhibited PTP1B activity with an IC₅₀ of 2.79 µM. Meanwhile, it had low cytotoxicity and enhanced glucose uptake in vitro. Further studies demonstrated that some of these active compounds had a specific selectivity over other PTPs. Computational analysis further showed the binding mode of compound 9f with the active pocket of PTP1B. Our studies provide a novel scaffold for further development of more promising PTP1B inhibitors and potential drugs for type II diabetes and obesity.