Design, synthesis, and biological evaluation of novel 8-substituted quercetin derivatives targeting the β‑catenin/B-cell lymphoma 9 interaction.

The β-catenin/B-cell lymphoma 9 (BCL9) protein-protein interaction (PPI) is a potential target for aberrantly active Wnt/β-catenin signaling which actively participates in initiating and progressing of many cancers. Herein, we discovered novel 8-substituted quercetin derivatives with potential inhibitory activities targeting β-catenin/BCL9 PPI. Among all the derivatives, compound B4 displayed the most promising PPI inhibitory activity with an IC value of 2.

Design, synthesis and biological evaluation of quercetin derivatives as novel β-catenin/B-cell lymphoma 9 protein-protein interaction inhibitors.

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 first described quercetin and its derivatives had potential inhibitory effects on β-catenin/BCL9 PPI. The most potent compound, quercetin-3'-O-(4-methylpiperazine-1-yl) propyl (C1), directly binded with β-catenin and disrupted the β-catenin/BCL9 interaction in both the protein level and the cellular context.

Microorganism, Carriers, and Immobilization Methods of the Microbial Self-Healing Cement-Based Composites: A Review.

Low tensile strength, poor elastic modulus, and complex concrete cracking work condition are almost unavoidable due to the intrinsic brittleness. To deal with concrete maintenance and durability, microbial self-healing concretes have been rapidly developed and widely applied recently. The microbial self-healing can specifically patch fractures as well as boost the concrete structure's capacity, durability, and permeability.

RORγt agonist synergizes with CTLA-4 antibody to inhibit tumor growth through inhibition of Treg cells via TGF-β signaling in cancer.

To date, the overall response rate to checkpoint blockade remains unsatisfactory, partially due to the limited understanding of the tumor immune microenvironment. The retinoic acid-related orphan receptor γt (RORγt) is the key transcription factor of T helper cell 17 (Th17) cells and plays an essential role in tumor immunity. In this study, we used JG-1, a potent and selective small-molecule RORγt agonist to evaluate the therapeutic potential and mechanism of action of targeting RORγt in tumor immunity.