LSM-42773 and Neoplasms

LSM-42773 has been researched along with Neoplasms* in 1 studies

Other Studies

1 other study(ies) available for LSM-42773 and Neoplasms

Article	Year
Discovery of Selective Small-Molecule Inhibitors for the β-Catenin/T-Cell Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone Moiety. Journal of medicinal chemistry, 2015, Jun-11, Volume: 58, Issue:11 Acyl hydrazone is an important functional group for the discovery of bioactive small molecules. This functional group is also recognized as a pan assay interference structure. In this study, a new small-molecule inhibitor for the β-catenin/Tcf protein-protein interaction (PPI), ZINC02092166, was identified through AlphaScreen and FP assays. This compound contains an acyl hydrazone group and exhibits higher inhibitory activities in cell-based assays than biochemical assays. Inhibitor optimization resulted in chemically stable derivatives that disrupt the β-catenin/Tcf PPI. The binding mode of new inhibitors was characterized by site-directed mutagenesis and structure-activity relationship studies. This series of inhibitors with a new scaffold exhibits dual selectivity for β-catenin/Tcf over β-catenin/cadherin and β-catenin/APC PPIs. One derivative of this series suppresses canonical Wnt signaling, downregulates the expression of Wnt target genes, and inhibits the growth of cancer cells. This compound represents a solid starting point for the development of potent and selective β-catenin/Tcf inhibitors. Topics: Antineoplastic Agents; beta Catenin; Blotting, Western; Cell Proliferation; Drug Discovery; Enzyme-Linked Immunosorbent Assay; HEK293 Cells; Humans; Hydrazones; Immunoprecipitation; Models, Molecular; Molecular Structure; Neoplasms; Protein Binding; Protein Interaction Maps; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Small Molecule Libraries; Structure-Activity Relationship; TCF Transcription Factors; Tumor Cells, Cultured; Wnt Signaling Pathway	2015

Article

Year

Discovery of Selective Small-Molecule Inhibitors for the β-Catenin/T-Cell Factor Protein-Protein Interaction through the Optimization of the Acyl Hydrazone Moiety.

Journal of medicinal chemistry, 2015, Jun-11, Volume: 58, Issue:11

Acyl hydrazone is an important functional group for the discovery of bioactive small molecules. This functional group is also recognized as a pan assay interference structure. In this study, a new small-molecule inhibitor for the β-catenin/Tcf protein-protein interaction (PPI), ZINC02092166, was identified through AlphaScreen and FP assays. This compound contains an acyl hydrazone group and exhibits higher inhibitory activities in cell-based assays than biochemical assays. Inhibitor optimization resulted in chemically stable derivatives that disrupt the β-catenin/Tcf PPI. The binding mode of new inhibitors was characterized by site-directed mutagenesis and structure-activity relationship studies. This series of inhibitors with a new scaffold exhibits dual selectivity for β-catenin/Tcf over β-catenin/cadherin and β-catenin/APC PPIs. One derivative of this series suppresses canonical Wnt signaling, downregulates the expression of Wnt target genes, and inhibits the growth of cancer cells. This compound represents a solid starting point for the development of potent and selective β-catenin/Tcf inhibitors.

Topics: Antineoplastic Agents; beta Catenin; Blotting, Western; Cell Proliferation; Drug Discovery; Enzyme-Linked Immunosorbent Assay; HEK293 Cells; Humans; Hydrazones; Immunoprecipitation; Models, Molecular; Molecular Structure; Neoplasms; Protein Binding; Protein Interaction Maps; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Small Molecule Libraries; Structure-Activity Relationship; TCF Transcription Factors; Tumor Cells, Cultured; Wnt Signaling Pathway

2015