1. Academic Validation
  2. Small-molecule synergist of the Wnt/beta-catenin signaling pathway

Small-molecule synergist of the Wnt/beta-catenin signaling pathway

  • Proc Natl Acad Sci U S A. 2007 May 1;104(18):7444-8. doi: 10.1073/pnas.0702136104.
Qisheng Zhang 1 Michael B Major Shinichi Takanashi Nathan D Camp Naoyuki Nishiya Eric C Peters Mark H Ginsberg Xiaoying Jian Paul A Randazzo Peter G Schultz Randall T Moon Sheng Ding
Affiliations

Affiliation

  • 1 Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Abstract

The Wnt/beta-catenin signaling pathway regulates cell fate and behavior during embryogenesis, adult tissue homeostasis, and regeneration. When inappropriately activated, the pathway has been linked to colorectal Cancer and melanoma, and when attenuated it may contribute to Alzheimer's disease and osteoporosis. Small molecules that modulate Wnt signaling will likely provide new insights into the regulation of this key developmental pathway and ultimately provide pharmacological agents to control Wnt signaling in vivo. To this end, we screened a library of 100,000 small molecules for activity in a cell-based assay of Wnt/beta-catenin signaling and discovered a purine derivative, QS11, that synergizes with Wnt-3a ligand in the activation of Wnt/beta-catenin signal transduction. Through affinity chromatography and subsequent functional assays, we showed that QS11 binds and inhibits the GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1), suggesting that QS11 modulates Wnt/beta-catenin signaling through an effect on protein trafficking. Consistent with its function as an ARFGAP inhibitor, QS11 inhibits migration of ARFGAP overexpressing breast Cancer cells.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-12762
    99.22%, ARFGAP1 抑制剂