Histone deacetylase (HDAC) inhibitors have been extensively studied in experimental models of cancer, where their inhibition of deacetylation has been proven to regulate cell survival, proliferation, differentiation and apoptosis. This in turn has led to the use of a variety of HDAC inhibitors in clinical trials. In recent years the applicability of HDAC inhibitors in other areas of disease has been explored, including the treatment of fibrotic disorders. Impaired wound healing involves the continuous deposition and cross-linking of extracellular matrix governed by myofibroblasts leading to diseases such as liver and kidney fibrosis; both diseases have high unmet medical needs which are a burden on health budgets worldwide. We provide an overview of the potential use of HDAC inhibitors against liver and kidney fibrosis using the current understanding of these inhibitors in experimental animal models and in vitro models of fibrosis.
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http://dx.doi.org/10.1186/1755-1536-6-1 | DOI Listing |
Lancet Neurol
February 2025
Department of Neurosciences, and Leuven Brain Institute, University of Leuven, Leuven, Belgium; Laboratory of Neurobiology, Center for Brain & Disease Research, VIB, Leuven, Belgium. Electronic address:
Autosomal dominant mutations in the gene encoding the DNA and RNA binding protein FUS are a cause of amyotrophic lateral sclerosis (ALS), and about 0·3-0·9% of patients with ALS are FUS mutation carriers. FUS-mutation-associated ALS (FUS-ALS) is characterised by early onset and rapid progression, compared with other forms of ALS. However, different pathogenic mutations in FUS can result in markedly different age at symptom onset and rate of disease progression.
View Article and Find Full Text PDFBioorg Chem
January 2025
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata 700026, India. Electronic address:
Histone deacetylases (HDACs) play a critical role in chromatin remodelling and modulating the activity of various histone proteins. Aberrant HDAC functions has been related to the progression of breast cancer (BC), making HDAC inhibitors (HDACi) promising small-molecule therapeutics for its treatment. Hydroxamic acid (HA) is a significant pharmacophore due to its strong metal-chelating ability, HDAC inhibition properties, MMP inhibition abilities, and more.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Drug and Health Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Precise binding free-energy predictions for ligands targeting metalloproteins, especially zinc-containing histone deacetylase (HDAC) enzymes, require specialized computational approaches due to the unique interactions at metal-binding sites. This study evaluates a docking algorithm optimized for zinc coordination to determine whether it could accurately differentiate between protonated and deprotonated states of hydroxamic acid ligands, a key functional group in HDAC inhibitors (HDACi). By systematically analyzing both protonation states, we sought to identify which state produces docking poses and binding energy estimates most closely aligned with experimental values.
View Article and Find Full Text PDFInt J Mol Sci
January 2025
Department of Pathogen Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
is a globally widespread pathogen of significant veterinary and medical importance, causing abortion or congenital disease in humans and other warm-blooded animals. Nevertheless, the current treatment options are restricted and sometimes result in toxic side effects. Hence, it is essential to discover drugs that demonstrate potent anti- activity.
View Article and Find Full Text PDFCancers (Basel)
January 2025
Eli Lilly and Company, Indianapolis, IN 46221, USA.
Small-cell lung cancer (SCLC) is a recalcitrant form of cancer, representing 15% of lung cancer cases globally. SCLC is classified within the range of neuroendocrine pulmonary neoplasms, exhibiting shared morphologic, ultrastructural, immunohistochemical, and molecular genomic features. It is marked by rapid proliferation, a propensity for early metastasis, and an overall poor prognosis.
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