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|Ref Type||Journal Article|
|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.|
|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.|
|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||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|
|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|