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.

Olfactory marker protein regulation of glucagon secretion in hyperglycemia.

The olfactory marker protein (OMP), which is also expressed in nonolfactory tissues, plays a role in regulating the kinetics and termination of olfactory transduction. Thus, we hypothesized that OMP may play a similar role in modulating the secretion of hormones involved in Ca and cAMP signaling, such as glucagon. In the present study, we confirmed nonolfactory α-cell-specific OMP expression in human and mouse pancreatic islets as well as in the murine α-cell line αTC1.

Synthesis and structure-activity relationship of thiol-based histone deacetylase 6 inhibitors.

Selective histone deacetylase 6 (HDAC6) inhibitors are safe and well-tolerated with less off-target effect. However, most available HDAC6 inhibitors contain hydroxamate as a zinc-binding group (ZBG), and their unfavorable pharmacokinetic properties along with potential genotoxicity limited wide application in diverse diseases. Therefore, we designed and synthesized a series of selective HDAC6 inhibitors utilizing thiol as the ZBG and discussed their structure-activity relationship based on molecular docking.

Recent advances in β-catenin/BCL9 protein-protein interaction inhibitors.

Wnt/β-catenin signaling is crucial both in normal embryonic development and throughout the life of an organism. Moreover, aberrant Wnt signaling has been associated with various diseases, especially cancer and fibrosis. Recent research suggests that direct targeting of the β-catenin/BCL9 protein-protein interaction (PPI) is a promising strategy to block the Wnt pathway.

Transcriptome analysis of Phelipanche aegyptiaca seed germination mechanisms stimulated by fluridone, TIS108, and GR24.

P. aegyptiaca is one of the most destructive root parasitic plants worldwide, causing serious damage to many crop species. Under natural conditions P.