Reference Detail

Ref Type

Journal Article

PMID

(14749129)

Authors

Lepourcelet M, Chen YN, France DS, Wang H, Crews P, Petersen F, Bruseo C, Wood AW, Shivdasani RA

Title

Small-molecule antagonists of the oncogenic Tcf/beta-catenin protein complex.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Cancer cell	5	1	2004 Jan	91-102	Cancer Cell

URL

Abstract Text

Key molecular lesions in colorectal and other cancers cause beta-catenin-dependent transactivation of T cell factor (Tcf)-dependent genes. Disruption of this signal represents an opportunity for rational cancer therapy. To identify compounds that inhibit association between Tcf4 and beta-catenin, we screened libraries of natural compounds in a high-throughput assay for immunoenzymatic detection of the protein-protein interaction. Selected compounds disrupt Tcf/beta-catenin complexes in several independent in vitro assays and potently antagonize cellular effects of beta-catenin-dependent activities, including reporter gene activation, c-myc or cyclin D1 expression, cell proliferation, and duplication of the Xenopus embryonic dorsal axis. These compounds thus meet predicted criteria for disrupting Tcf/beta-catenin complexes and define a general standard to establish mechanism-based activity of small molecule inhibitors of this pathogenic protein-protein interaction.

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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

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	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	colon cancer	sensitive	CGP049090	Preclinical	Actionable	In a preclinical study, CGP049090 inhibited proliferation of a colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129).	14749129
APC inact mut	colon cancer	sensitive	PKF115-584	Preclinical	Actionable	In a preclinical study, PKF115-584 inhibited proliferation of colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129).	14749129
APC inact mut	colorectal cancer	sensitive	PKF118-310	Preclinical	Actionable	In a preclinical study, PKF118-310 inhibited proliferation of colorectal cancer cell line harboring an APC inactivating mutation in culture (PMID: 14749129).	14749129