ArticleScientific reports2016
A Rational Approach for the Identification of Non-Hydroxamate HDAC6-Selective Inhibitors.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 37 citations in OpenAlex.
- Discovery of a Promising Hydroxyamino-Piperidine HDAC6 Inhibitor via Integrated Virtual Screening and Experimental Validation in Multiple Myeloma.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Drug Discovery for Histone Deacetylase Inhibition: Past, Present and Future of Zinc-Binding Groups.Pharmaceuticals (Basel, Switzerland) · 2025Review
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Discovery of novel SARS-CoV-2 inhibitors targeting the main protease MAntiviral research · 2022Article
- Pharmacophore-Based Discovery of Substrates of a Novel Drug/Proton-Antiporter in the Human Brain Endothelial hCMEC/D3 Cell Line.Pharmaceutics · 2022Article
- Article
- Multi-target weapons: diaryl-pyrazoline thiazolidinediones simultaneously targeting VEGFR-2 and HDAC cancer hallmarks.RSC medicinal chemistry · 2021Article
- Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases.Molecules (Basel, Switzerland) · 2021Review
- A novel orally active HDAC6 inhibitor T-518 shows a therapeutic potential for Alzheimer's disease and tauopathy in mice.Scientific reports · 2021Article
- An ELISA method to assess HDAC inhibitor-induced alterations to P. falciparum histone lysine acetylation.International journal for parasitology. Drugs and drug resistance · 2020Article
- Design, synthesis and biological evaluation of a series of CNS penetrant HDAC inhibitors structurally derived from amyloid-β probes.Scientific reports · 2019Article
- Natural Compounds and Their Analogues as Potent Antidotes against the Most Poisonous Bacterial Toxin.Applied and environmental microbiology · 2018Article
- Computer Aided Drug Design and its Application to the Development of Potential Drugs for Neurodegenerative Disorders.Current neuropharmacology · 2018Review
- Cellular analysis of the action of epigenetic drugs and probes.Epigenetics · 2017Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human histone deacetylase isoform 6 (HDAC6) has been demonstrated to play a major role in cell motility and aggresome formation, being interesting for the treatment of multiple tumour types and neurodegenerative conditions. Currently, most HDAC inhibitors in preclinical or clinical evaluations are non-selective inhibitors, characterised by a hydroxamate zinc-binding group (ZBG) showing off-target effects and mutagenicity. The identification of selective HDAC6 inhibitors with novel chemical properties has not been successful yet, also because of the absence of crystallographic information that makes the rational design of HDAC6 selective inhibitors difficult. Using HDAC inhibitory data retrieved from the ChEMBL database and ligand-based computational strategies, we identified 8 original new non-hydroxamate HDAC6 inhibitors from the SPECS database, with activity in the low μM range. The most potent and selective compound, bearing a hydrazide ZBG, was shown to increase tubulin acetylation in human cells. No effects on histone H4 acetylation were observed. To the best of our knowledge, this is the first report of an HDAC6 selective inhibitor bearing a hydrazide ZBG. Its capability to passively cross the blood-brain barrier (BBB), as observed through PAMPA assays, and its low cytotoxicity in vitro, suggested its potential for drug development.
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