Reference Detail

Ref Type Journal Article
PMID (21199802)
Authors Waaler J, Machon O, von Kries JP, Wilson SR, Lundenes E, Wedlich D, Gradl D, Paulsen JE, Machonova O, Dembinski JL, Dinh H, Krauss S
Title Novel synthetic antagonists of canonical Wnt signaling inhibit colorectal cancer cell growth.
Journal Cancer research
Vol 71
Issue 1
Date 2011 Jan 01
URL
Abstract Text Canonical Wnt signaling is deregulated in several types of human cancer where it plays a central role in tumor cell growth and progression. Here we report the identification of 2 new small molecules that specifically inhibit canonical Wnt pathway at the level of the destruction complex. Specificity was verified in various cellular reporter systems, a Xenopus double-axis formation assay and a gene expression profile analysis. In human colorectal cancer (CRC) cells, the new compounds JW67 and JW74 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1. Notably, AXIN2 protein levels were strongly increased after compound exposure. Long-term treatment with JW74 inhibited the growth of tumor cells in both a mouse xenograft model of CRC and in Apc(Min) mice (multiple intestinal neoplasia, Min). Our findings rationalize further preclinical and clinical evaluation of these new compounds as novel modalities for cancer treatment.

Filtering

  • Case insensitive filtering will display rows where any text in any cell matches the filter term
  • Simple literal full or partial string matches
  • Separate multiple filter terms with a spaces, order doesn't matter (a b c and c b a are equivalent )
  • Filtering will only apply to rows that are already loaded on the page, filtering has no impact on query parameters
  • Use quotes to match a longer phrase which contains spaces "mtor c1483f"

Sorting

  • Generally, the default sort order for tables is set to be first column ascending, however, specific tables may set a different default sort order.
  • Click on any column header arrows to sort by that column
  • Hold down the Shift key and click multiple columns to sort by more than one column, be sure to set ascending or descending order for a given column, before moving on to the next column.

Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Therapy Description
JW67 JW67 is a small molecule that inhibits canonical Wnt signaling, potentially resulting in decreased tumor cell growth (PMID: 21199802).
JW74 JW74 is a small molecule that inhibits canonical Wnt signaling, potentially resulting in decreased tumor cell growth (PMID: 21199802).
Drug Name Trade Name Synonyms Drug Classes Drug Description
JW67 CTNNB1 Inhibitor 26 JW67 is a small molecule that inhibits canonical Wnt signaling, potentially resulting in decreased tumor cell growth (PMID: 21199802).
JW74 CTNNB1 Inhibitor 26 JW74 is a small molecule that inhibits canonical Wnt signaling, potentially resulting in decreased tumor cell growth (PMID: 21199802).
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
APC Q1338* colorectal cancer sensitive JW67 Preclinical Actionable In a preclinical study, JW67 inhibited Wnt signaling and decreased proliferation of colorectal cancer cells harboring APC Q1338* in culture (PMID: 21199802). 21199802
APC mutant colorectal cancer sensitive JW74 Preclinical Actionable In a preclinical study, JW74 reduced tumor formation and growth in a mouse model of colorectal cancer harboring an APC mutation (PMID: 21199802). 21199802
APC Q1338* colorectal cancer sensitive JW74 Preclinical Actionable In a preclinical study, JW74 inhibited Wnt signaling and decreased growth of colorectal cancer cells harboring APC Q1338* in culture and in xenograft models (PMID: 21199802). 21199802