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|Ref Type||Journal Article|
|Authors||Tian W, Han X, Yan M, Xu Y, Duggineni S, Lin N, Luo G, Li YM, Han X, Huang Z, An J|
|Title||Structure-based discovery of a novel inhibitor targeting the β-catenin/Tcf4 interaction.|
|Date||2012 Jan 17|
|Abstract Text||Overactivation or overexpression of β-catenin in the Wnt (wingless) signaling pathway plays an important role in tumorigenesis. Interaction of β-catenin with T-cell factor (Tcf) DNA binding proteins is a key step in the activation of the proliferative genes in response to upstream signals of this Wnt/β-catenin pathway. Recently, we identified a new small molecule inhibitor, named BC21 (C(32)H(36)Cl(2)Cu(2)N(2)O(2)), which effectively inhibits the binding of β-catenin with Tcf4-derived peptide and suppresses β-catenin/Tcf4 driven reporter gene activity. This inhibitor decreases the viability of β-catenin overexpressing HCT116 colon cancer cells that harbor the β-catenin mutation, and more significantly, it inhibits the clonogenic activity of these cells. Down-regulation of c-Myc and cyclin D1 expression, the two important effectors of the Wnt/β-catenin signaling, is confirmed by treating HCT116 cells with BC21. This compound represents a new and modifiable potential anticancer candidate that targets β-catenin/Tcf-4 interaction.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|BC21||CTNNB1 Inhibitor 26||BC21 inhibits the interaction of CTNNB1 with TCF7L2 to block Wnt signaling, which can prevent cell proliferation and induce apoptosis (PMID: 22224445).|
|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|
|CTNNB1 mutant||colorectal cancer||sensitive||BC21||Preclinical||Actionable||In a preclinical study, BC21 inhibited growth and viability of a colorectal cancer cell line with a CTNNB1 mutation and increased beta-catenin expression in culture (PMID: 22224445).||22224445|