4395-74-8Relevant academic research and scientific papers
SMALL-MOLECULE INHIBITORS FOR THE Β-CATENIN/B-CELL LYMPHOMA 9 PROTEIN?PROTEIN INTERACTION
-
Page/Page column 51; 144, (2021/04/01)
Disclosed are inhibitors for the β-catenin/B-cell lymphoma 9 interaction. The inhibitors are selective for β-catenin/B-cell lymphoma 9 over β-catenin/ E-cadherin PPI interaction. Methods of using the disclosed compounds to treat cancer are also disclosed.
Discovery of 2-(3-(3-Carbamoylpiperidin-1-yl)phenoxy)acetic Acid Derivatives as Novel Small-Molecule Inhibitors of the β-Catenin/B-Cell Lymphoma 9 Protein-Protein Interaction
Wang, Zhen,Zhang, Min,Luo, Wen,Zhang, Yongqiang,Ji, Haitao
, p. 5886 - 5904 (2021/06/01)
The β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for the suppression of hyperactive Wnt/β-catenin signaling that is vigorously involved in cancer initiation and development. Herein, we describe the medicinal chemistry optimization of a screening hit to yield novel small-molecule inhibitors of the β-catenin/BCL9 interaction. The best compound 30 can disrupt the β-catenin/BCL9 interaction with a Ki of 3.6 μM in AlphaScreen competitive inhibition assays. Cell-based experiments revealed that 30 selectively disrupted the β-catenin/BCL9 PPI, while leaving the β-catenin/E-cadherin PPI unaffected, dose-dependently suppressed Wnt signaling transactivation, downregulated oncogenic Wnt target gene expression, and on-target selectively inhibited the growth of cancer cells harboring aberrant Wnt signaling. This compound with a new chemotype can serve as a lead compound for further optimization of inhibitors for β-catenin/BCL9 PPI.
