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J Am Chem Soc. 2013 Feb 6;135(5):1669-72. doi: 10.1021/ja309304m. Epub 2013 Jan 25.

Small-molecule inducer of β cell proliferation identified by high-throughput screening.

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1
Department of Chemistry, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, California 92037, United States.

Erratum in

  • J Am Chem Soc. 2013 Mar 20;135(11):4573.

Abstract

The identification of factors that promote β cell proliferation could ultimately move type 1 diabetes treatment away from insulin injection therapy and toward a cure. We have performed high-throughput, cell-based screens using rodent β cell lines to identify molecules that induce proliferation of β cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes β cell proliferation in rodent and human primary islets. In the RIP-DTA mouse model of β cell ablation, WS6 normalized blood glucose and induced concomitant increases in β cell proliferation and β cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the IκB kinase pathway in the mechanism of action of WS6.

PMID:
23330637
DOI:
10.1021/ja309304m
[Indexed for MEDLINE]

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