Small-Molecule Inducer of 尾 Cell Proliferation Identified by High-Throughput Screening

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• 作者：Weijun Shen ; 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
• 刊名：The Journal of the American Chemical Society
• 出版年：2013
• 出版时间：February 6, 2013
• 年：2013
• 卷：135
• 期：5
• 页码：1669-1672
• 全文大小：308K
• 年卷期：v.135,no.5(February 6, 2013)
• ISSN：1520-5126

文摘

The identification of factors that promote 尾 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 尾 cell lines to identify molecules that induce proliferation of 尾 cells. Herein we report the discovery and characterization of WS6, a novel small molecule that promotes 尾 cell proliferation in rodent and human primary islets. In the RIP-DTA mouse model of 尾 cell ablation, WS6 normalized blood glucose and induced concomitant increases in 尾 cell proliferation and 尾 cell number. Affinity pulldown and kinase profiling studies implicate Erb3 binding protein-1 and the I魏B kinase pathway in the mechanism of action of WS6.