Small molecule modulators of Wnt/β-catenin signaling.

Journal Article

The Wnt signal transduction pathway is dysregulated in many highly prevalent diseases, including cancer. Unfortunately, drug discovery efforts have been hampered by the paucity of targets and drug-like lead molecules amenable to drug discovery. Recently, we reported the FDA-approved anthelmintic drug Niclosamide inhibits Wnt/β-catenin signaling by a unique mechanism, though the target responsible remains unknown. We interrogated the mechanism and structure-activity relationships to understand drivers of potency and to assist target identification efforts. We found inhibition of Wnt signaling by Niclosamide appears unique among the structurally-related anthelmintic agents tested and found the potency and functional response was dependent on small changes in the chemical structure of Niclosamide. Overall, these findings support efforts to identify the target of Niclosamide inhibition of Wnt/β-catenin signaling and the discovery of potent and selective modulators to treat human disease.

Full Text

Duke Authors

Cited Authors

  • Mook, RA; Chen, M; Lu, J; Barak, LS; Lyerly, HK; Chen, W

Published Date

  • April 1, 2013

Published In

Volume / Issue

  • 23 / 7

Start / End Page

  • 2187 - 2191

PubMed ID

  • 23453073

Electronic International Standard Serial Number (EISSN)

  • 1464-3405

Digital Object Identifier (DOI)

  • 10.1016/j.bmcl.2013.01.101

Language

  • eng

Conference Location

  • England