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Cyanoacrylates define a class of inhibitors which are capable to form a transient covalent bond with a cysteine flanking the binding site, thereby increasing the residence time and prolonging the inhibitory effect on the target protein under nonequilibrium conditions. Herein, we describe the synthetic access to cyanoacrylate-based HDAC4 inhibitors and the procedures for the characterization of the transient nature of the covalent bond between cyanoacrylates and thiols or cysteines in HDAC4.
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http://dx.doi.org/10.1007/978-1-0716-2788-4_14 | DOI Listing |
Int J Mol Med
October 2025
College of Rehabilitation Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250355, P.R. China.
Cardiovascular disease (CVD) is a major global health threat, as its incidence and mortality rates continue to rise, highlighting the urgent need for effective therapeutic strategies. Histone deacetylase 4 (HDAC4), a member of class IIa HDACs, has attracted increasing attention in recent years for its role in CVD. Studies have shown that HDAC4 can influence the development and progression of CVD such as cardiac hypertrophy, hypertension and atherosclerosis by regulating key pathophysiological processes including inflammation, fibrosis and apoptosis.
View Article and Find Full Text PDFFASEB Bioadv
August 2025
Division of Pharmacology, Department of Neuroscience, Reproductive and Dentistry Sciences, School of Medicine Federico II University of Naples Naples Italy.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) is associated with neurological symptoms, but the molecular mechanisms have not yet been identified. Since the S1 subunit (S1) of the envelope of the SARS-CoV2 Spike glycoprotein can reach the CNS, we studied whether S1 could cause neuronal death in a direct manner. Transfection of the S1 plasmid in SH-SY5Y cells reduces cell survival in a time-dependent manner, whereas the overexpression of the S2 subunit does not.
View Article and Find Full Text PDFFuture Med Chem
July 2025
Department of Pharmacology and Toxicology, College of Pharmacy, Jazan University, Jazan, Saudi Arabia.
Epigenetic therapy and targeted protein degradation have converged in the development of histone deacetylases (HDACs)-targeting proteolysis-targeting chimeras (PROTACs), offering a novel approach to cancer treatment. Unlike traditional HDAC inhibitors, HDAC-PROTACs facilitate selective degradation of HDACs via the ubiquitin-proteasome system, effectively eliminating both enzymatic and scaffolding functions. These bifunctional molecules recruit HDACs to E3 ligases, triggering ubiquitination and subsequent proteasomal degradation.
View Article and Find Full Text PDFInvest Ophthalmol Vis Sci
July 2025
Department of Microbiology, Faculty of Science, Chulalongkorn University, Bangkok, Thailand.
Purpose: The purpose of this study was to investigate fibroblast markers and histone deacetylase (HDAC) 4 in orbital tissues and orbital fibroblasts from patients with Graves' ophthalmopathy (GO) and healthy controls.
Methods: Hematoxylin and eosin (H&E), Masson's trichrome, and Verhoeff's Van Gieson (VVG) staining were performed on GO and control orbital tissues. Immunohistochemistry on fibroblast markers were investigated.
J Mol Biol
October 2025
Brain Science Institute, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science & Technology, KIST School, University of Science and Technology (UST), Seoul 02792,Republic of Korea. Electronic address:
TDP-43 proteinopathies, including amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD), are characterized by aberrant cytoplasmic mislocalization and aggregation of TDP-43. Here, we established a live-cell TDP43-BiFC model to visualize TDP-43 oligomerization in real time and screened diverse cellular stressors. Histone deacetylase (HDAC) inhibition emerged as the most potent trigger of TDP-43 oligomerization.
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