2. Academic Validation
  3. Small-molecule inducer of β cell proliferation identified by high-throughput screening

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

Affiliation

  • 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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