title: Small-molecule inducer of β cell proliferation identified by high-throughput screening.
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.
authors: Department of Chemistry, 10550 North Torrey Pines Road, The Scripps Research Institute, La Jolla, California 92037, United States.
authors: Weijun
authors: W
authors: Shen
authors: Matthew S
authors: MS
authors: Tremblay
authors: Vishal A
authors: VA
authors: Deshmukh
authors: Weidong
authors: W
authors: Wang
authors: Christophe M
authors: CM
authors: Filippi
authors: George
authors: G
authors: Harb
authors: You-qing
authors: YQ
authors: Zhang
authors: Anwesh
authors: A
authors: Kamireddy
authors: Janine E
authors: JE
authors: Baaten
authors: Qihui
authors: Q
authors: Jin
authors: Tom
authors: T
authors: Wu
authors: Jonathan G
authors: JG
authors: Swoboda
authors: Charles Y
authors: CY
authors: Cho
authors: Jing
authors: J
authors: Li
authors: Bryan A
authors: BA
authors: Laffitte
authors: Peter
authors: P
authors: McNamara
authors: Richard
authors: R
authors: Glynne
authors: Xu
authors: X
authors: Wu
authors: Ann E
authors: AE
authors: Herman
authors: Peter G
authors: PG
authors: Schultz
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057166:High-Throughput Screening Assays; D006801:Humans; D007515:Islets of Langerhans / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D015394:Molecular Structure; D008970:Molecular Weight; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014508:Urea