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Inhibiting the Wnt Signaling Pathway with Small Molecules

  • Ho-Jin Lee
  • Xinxin Zhang
  • Jie J. ZhengEmail author
Chapter

Abstract

Wnt signaling plays important roles in embryonic development and in maintenance of adult tissues. Mutation, loss, or overexpression of key Wnt pathway components has been linked to various types of cancer. Therefore, inhibition of Wnt signaling is of interest for the development of novel anticancer agents. The results of recent structure-based screening, high-throughput screening (HTS), and chemical genomics studies demonstrate that small molecules, including synthetic and natural compounds, can inhibit Wnt signaling in various cancers by blocking specific protein–protein interactions or the activity of specific enzymes. In biological studies, these compounds appear promising as potential anticancer agents; however, their efficacy and toxicity have yet to be investigated. Small molecule inhibitors of Wnt signaling also have wide-ranging potential as tools for elucidating disease and basic biology. Indubitably, in the near future, these compounds will yield agents that are clinically useful against malignant diseases.

Keywords

Ethacrynic Acid EGCG Treatment Quercetin Treatment SW480 Colon Cancer Cell Sulindac Sulfone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

APC

Adenomatous polyposis coli

CK1

Casein kinase 1

CLL

Chronic lymphocytic leukemia

COX

Cyclooxygenase

CRC

Colon carcinoma

DEP

Dishevelled Egl-10, and pleckstrin

DIX

Dishevelled and axin

Dvl/Dsh

Dishevelled

EA

Ethacrynic acid

Fz

Frizzled

GSK-3β

Glycogen synthase kinase-3

HTS

High-throughput screening

LRP

Low-density lipoprotein receptor (LDLR)-related protein

MM

Multiple myeloma

NMR

Nuclear magnetic resonance

NSAIDs

Nonsteroidal anti-inflammatory drugs

NSCLC

Nonsmall cell lung cancer

PPAR-γ

Peroxisome proliferator-activated receptor γ

Notes

Acknowledgments

We thank Sharon Naron for editorial help. This work is supported by the American Lebanese Syrian Associated Charities, by the Cancer Center Support Grant (CA21765) from the National Cancer Institute, and by National Institutes of Health Grant GM081492.

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Structural BiologySt. Jude Children’s Research HospitalMemphisUSA

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