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A small molecule inducer of β cell proliferation identified by high-throughput screening

Glynne, Richard and Mcnamara, Peter and Laffitte, Bryan and Li, Jing and Wu, Tom and Jin, Qihui and Baaten, Janine and Cho, Charles and Kamireddy, Anwesh and Zhang, You-Qing and Harb, George and Filippi, Christophe and Shen, Weijun and Tremblay, Matthew and Deshmukh, Vishal and Wang, Weidong and Swoboda, Jonathan and Wu, Xu and Herman, Ann and Schultz, Peter (2013) A small molecule inducer of β cell proliferation identified by high-throughput screening. Journal of the American Chemical Society, 135 (5). pp. 1669-1672. ISSN 0002-7863

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.

Item Type: Article
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Date Deposited: 13 Oct 2015 13:13
Last Modified: 13 Oct 2015 13:13
URI: https://oak.novartis.com/id/eprint/9363

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