Unknown

Dataset Information

0

Structure-Based Design of 1,4-Dibenzoylpiperazines as ?-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction Inhibitors.

ABSTRACT: A small-molecule inhibitor with a 1,4-dibenzoylpiperazine scaffold was designed to match the critical binding elements in the ?-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction interface. Inhibitor optimization led to a potent inhibitor that can disrupt the ?-catenin/BCL9 interaction and exhibit 98-fold selectivity over the ?-catenin/cadherin interaction. The binding mode of new inhibitors was characterized by structure-activity relationships and site-directed mutagenesis studies. Cell-based studies demonstrated that this series of inhibitors can selectively suppress canonical Wnt signaling and inhibit growth of Wnt/?-catenin-dependent cancer cells.

SUBMITTER: Wisniewski JA 

PROVIDER: S-EPMC4867476 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

Structure-Based Design of 1,4-Dibenzoylpiperazines as β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction Inhibitors.

Wisniewski John A JA   Yin Jinya J   Teuscher Kevin B KB   Zhang Min M   Ji Haitao H  

ACS medicinal chemistry letters 20160328 5

A small-molecule inhibitor with a 1,4-dibenzoylpiperazine scaffold was designed to match the critical binding elements in the β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction interface. Inhibitor optimization led to a potent inhibitor that can disrupt the β-catenin/BCL9 interaction and exhibit 98-fold selectivity over the β-catenin/cadherin interaction. The binding mode of new inhibitors was characterized by structure-activity relationships and site-directed mutagenesis studies. Ce  ...[more]

Similar Datasets

Unknown Structure-Based Optimization of Small-Molecule Inhibitors for the ?-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction.
| S-EPMC7787347 | biostudies-literature
Unknown Structure-based design of small peptide inhibitors of protein kinase CK2 subunit interaction.
| S-EPMC2267368 | biostudies-literature
Unknown Inhibition of β-catenin/B cell lymphoma 9 protein-protein interaction using α-helix-mimicking sulfono-γ-AApeptide inhibitors.
| S-EPMC6561201 | biostudies-literature
Unknown Design of triazole-stapled BCL9 ?-helical peptides to target the ?-catenin/B-cell CLL/lymphoma 9 (BCL9) protein-protein interaction.
| S-EPMC3286869 | biostudies-literature
Unknown Optimization of Peptidomimetics as Selective Inhibitors for the ?-Catenin/T-Cell Factor Protein-Protein Interaction.
| S-EPMC6931396 | biostudies-literature
Unknown Structure-Based Design of Conformationally Constrained, Cell-Permeable STAT3 Inhibitors.
| S-EPMC2892918 | biostudies-literature
Unknown Structure-Based Design of Inhibitors of Protein-Protein Interactions: Mimicking Peptide Binding Epitopes.
| S-EPMC4557054 | biostudies-literature
Unknown Structure-based design of ricin inhibitors.
| S-EPMC3210460 | biostudies-literature
Unknown Structure Based Design of Potent Selective Inhibitors of Protein Kinase D1 (PKD1).
| S-EPMC6746091 | biostudies-literature
Unknown Structure-based design of covalent Siah inhibitors.
| S-EPMC3763817 | biostudies-literature