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

  • J Am Chem Soc. 2013 Feb 6;135(5):1669-72. doi: 10.1021/ja309304m.
Weijun Shen  1 ,  Matthew S Tremblay ,  Vishal A Deshmukh ,  Weidong Wang ,  Christophe M Filippi ,  George Harb ,  You-qing Zhang ,  Anwesh Kamireddy ,  Janine E Baaten ,  Qihui Jin ,  Tom Wu ,  Jonathan G Swoboda ,  Charles Y Cho ,  Jing Li ,  Bryan A Laffitte ,  Peter McNamara ,  Richard Glynne ,  Xu Wu ,  Ann E Herman ,  Peter G Schultz
Affiliations
  • 1. Department of Chemistry, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, California 92037, United States.
PMID: 23330637 DOI: 10.1021/ja309304m
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.

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