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Small molecule modulators of Wnt/β-catenin signaling.

Publication ,  Journal Article
Mook, RA; Chen, M; Lu, J; Barak, LS; Lyerly, HK; Chen, W
Published in: Bioorg Med Chem Lett
April 1, 2013

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.

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Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

April 1, 2013

Volume

23

Issue

7

Start / End Page

2187 / 2191

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt Signaling Pathway
  • Structure-Activity Relationship
  • Small Molecule Libraries
  • Niclosamide
  • Molecular Structure
  • Medicinal & Biomolecular Chemistry
  • Humans
  • HEK293 Cells
  • Dose-Response Relationship, Drug
 

Citation

APA
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MLA
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Mook, R. A., Chen, M., Lu, J., Barak, L. S., Lyerly, H. K., & Chen, W. (2013). Small molecule modulators of Wnt/β-catenin signaling. Bioorg Med Chem Lett, 23(7), 2187–2191. https://doi.org/10.1016/j.bmcl.2013.01.101
Mook, Robert A., Minyong Chen, Jiuyi Lu, Larry S. Barak, H Kim Lyerly, and Wei Chen. “Small molecule modulators of Wnt/β-catenin signaling.Bioorg Med Chem Lett 23, no. 7 (April 1, 2013): 2187–91. https://doi.org/10.1016/j.bmcl.2013.01.101.
Mook RA, Chen M, Lu J, Barak LS, Lyerly HK, Chen W. Small molecule modulators of Wnt/β-catenin signaling. Bioorg Med Chem Lett. 2013 Apr 1;23(7):2187–91.
Mook, Robert A., et al. “Small molecule modulators of Wnt/β-catenin signaling.Bioorg Med Chem Lett, vol. 23, no. 7, Apr. 2013, pp. 2187–91. Pubmed, doi:10.1016/j.bmcl.2013.01.101.
Mook RA, Chen M, Lu J, Barak LS, Lyerly HK, Chen W. Small molecule modulators of Wnt/β-catenin signaling. Bioorg Med Chem Lett. 2013 Apr 1;23(7):2187–2191.
Journal cover image

Published In

Bioorg Med Chem Lett

DOI

EISSN

1464-3405

Publication Date

April 1, 2013

Volume

23

Issue

7

Start / End Page

2187 / 2191

Location

England

Related Subject Headings

  • beta Catenin
  • Wnt Signaling Pathway
  • Structure-Activity Relationship
  • Small Molecule Libraries
  • Niclosamide
  • Molecular Structure
  • Medicinal & Biomolecular Chemistry
  • Humans
  • HEK293 Cells
  • Dose-Response Relationship, Drug