Herein we report on the multicomponent synthesis of a novel imidazole-based compound, able to act efficiently as a minimalist β-strand mimic. Biological evaluation proved its ability to impair the LDLR-PCSK9 protein-protein interaction, disclosing it as the first small molecule exerting a PCSK9-mediated hypocholesterolemic effect.
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http://dx.doi.org/10.1039/c6ob01642a | DOI Listing |
Sci Rep
January 2025
Department of Gastroenterology, the Second Hospital of Dalian Medical University, Dalian, 116021, China.
The constantly emerging evidence indicates a close association between coronary artery disease (CAD) and non-alcoholic fatty liver disease (NAFLD). However, the exact mechanisms underlying their mutual relationship remain undefined. This study aims to explore the common signature genes, potential mechanisms, diagnostic markers, and therapeutic targets for CAD and NAFLD.
View Article and Find Full Text PDFJ Ovarian Res
January 2025
Department of Reproductive Medicine Center, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, China.
Background: Polycystic ovary syndrome (PCOS) is an endocrine disease associated with reproductive and metabolic abnormalities. The aim of this study was to elucidate the effects of Schisandra rubriflora (S. rubriflora) on PCOS and its related mechanisms using network pharmacology, molecular docking and in vitro experiments.
View Article and Find Full Text PDFJ Am Chem Soc
January 2025
Laboratory of Chemical Biology, Department of Biomedical Engineering and Institute for Complex Molecular Systems, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands.
Misregulation of protein-protein interactions (PPIs) underlies many diseases; hence, molecules that stabilize PPIs, known as molecular glues, are promising drug candidates. Identification of novel molecular glues is highly challenging among others because classical biochemical assays in dilute aqueous conditions have limitations for evaluating weak PPIs and their stabilization by molecular glues. This hampers the systematic discovery and evaluation of molecular glues.
View Article and Find Full Text PDFRedox Biol
January 2025
Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China; Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, China. Electronic address:
Available evidence indicates that neuregulin-1 (NRG-1) can provide a protection against myocardial ischemia/reperfusion (I/R) injury and is involved in various cardioprotective interventions by potential regulation of mitophagy. However, the molecular mechanisms linking NRG-1 and mitophagy remain to be clarified. In this study, both an in vivo myocardial I/R injury model of rats and an in vitro hypoxia/reoxygenation (H/R) model of H9C2 cardiomyocytes were applied to determine whether NRG-1 postconditioning attenuated myocardial I/R injury through the regulation of mitophagy and to explore the underlying mechanisms.
View Article and Find Full Text PDFInt Immunopharmacol
January 2025
Department of Orthopaedics, Shanghai Jing'an District Zhabei Central Hospital, Shanghai 200070 China. Electronic address:
Background And Objectives: Intervertebral disc degeneration (IVDD) is a complex condition that necessitates the development of novel therapeutic strategies. The objective of this study was to investigate the therapeutic potential of Fuzi decoction (FZD) in the treatment of IVDD by examining its bioactive components, target genes, molecular interactions, pathways, and therapeutic efficacy.
Methods: Bioactive ingredients with an oral bioavailability (OB) of ≥ 30 % and drug likeness (DL) of ≥ 0.
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