Reference Detail

Ref Type Journal Article
PMID (20610623)
Authors Ewan K, Pajak B, Stubbs M, Todd H, Barbeau O, Quevedo C, Botfield H, Young R, Ruddle R, Samuel L, Battersby A, Raynaud F, Allen N, Wilson S, Latinkic B, Workman P, McDonald E, Blagg J, Aherne W, Dale T
Title A useful approach to identify novel small-molecule inhibitors of Wnt-dependent transcription.
Journal Cancer research
Vol 70
Issue 14
Date 2010 Jul 15
URL
Abstract Text The Wnt signaling pathway is frequently deregulated in cancer due to mutations in genes encoding APC, beta-catenin, and axin. To identify small-molecule inhibitors of Wnt signaling as potential therapeutics, a diverse chemical library was screened using a transcription factor reporter cell line in which the activity of the pathway was induced at the level of Disheveled protein. A series of deconvolution studies was used to focus on three compound series that selectively killed cancer cell lines with constitutive Wnt signaling. Activities of the compounds included the ability to induce degradation of beta-catenin that had been stabilized by a glycogen synthase kinase-3 (GSK-3) inhibitor. This screen illustrates a practical approach to identify small-molecule inhibitors of Wnt signaling that can seed the development of agents suitable to treat patients with Wnt-dependent tumors.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
CCT031374 CCT031374 1 0
CCT036477 CCT036477 1 0
CCT070535 CCT070535 1 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
CCT031374 CTNNB1 Inhibitor 26 CCT031374 inhibits TCF/CTNNB1 dependent transcription thereby blocking Wnt signaling, which results in apoptosis (PMID: 20610623).
CCT036477 CTNNB1 Inhibitor 26 CCT036477 inhibits TCF/CTNNB1 dependent transcription thereby blocking Wnt signaling, which results in apoptosis (PMID: 20610623).
CCT070535 CTNNB1 Inhibitor 26 CCT070535 inhibits TCF/CTNNB1 dependent transcription thereby blocking Wnt signaling, which results in apoptosis (PMID: 20610623).
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 inact mut colorectal cancer sensitive CCT031374 Preclinical Actionable In a preclinical study, CCT031374 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). 20610623
APC inact mut colorectal cancer sensitive CCT070535 Preclinical Actionable In a preclinical study, CCT070535 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). 20610623
APC inact mut colorectal cancer sensitive CCT036477 Preclinical Actionable In a preclinical study, CCT036477 inhibited Wnt pathway activation and growth of colorectal cancer cell lines harboring APC inactivating mutations in culture (PMID: 20610623). 20610623