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

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.

Although protein tyrosine phosphatase 1B (PTP1B) has been proposed as an effective target for the treatment of type II diabetes and obesity, no PTP1B inhibitor is applied in clinical practice. The mixed 3,3’‐bisindoles reported here have low PTP1B inhibitory activity in the micromolar range, with low cytotoxicity and enhanced glucose uptake in vitro. The novel scaffold may be used to develop more promising PTP1B inhibitors and potential drugs for type II diabetes and obesity.

Autoren:   Changcheng Jing, Ziyan Li, Kaili Jia, Chen Chen, Xiao Liu, Beibei Wang, Wenhao Hu, Jia Li, Tong Zhu, Suzhen Dong
Journal:   Archiv der Pharmazie
Jahrgang:   2016
Seiten:   n/a
DOI:   10.1002/ardp.201600173
Erscheinungsdatum:   28.12.2016
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