ArticleJournal of medicinal chemistry2015
Dual-Mode HDAC Prodrug for Covalent Modification and Subsequent Inhibitor Release.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 40 citations in OpenAlex.
- The radiosensitizing effects of a STAT3/HDAC dual-target inhibitor derived from isoalantolactone in solid tumor models.BMC cancer · 2026Article
- Epigenetics, bacterial metabolites and type 2 diabetes: a new view of gut-genome interactions.Frontiers in microbiology · 2026Review
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Review
- Complexation of histone deacetylase inhibitor belinostat to Cu(II) prevents premature metabolic inactivation in vitro and demonstrates potent anti-cancer activity in vitro and ex vivo in colon cancer.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Proteome-Wide Profiling of the Covalent-Druggable Cysteines with a Structure-Based Deep Graph Learning Network.Research (Washington, D.C.) · 2022Article
- Zap-Pano: a Photocaged Prodrug of the KDAC Inhibitor Panobinostat.ChemMedChem · 2021Article
- An ether-linked halogenated phenazine-quinone prodrug model for antibacterial applications.Organic & biomolecular chemistry · 2021Article
- Irreversible inhibition of BoNT/A protease: proximity-driven reactivity contingent upon a bifunctional approach.RSC medicinal chemistry · 2021Article
- Binding Free Energy (BFE) Calculations and Quantitative Structure-Activity Relationship (QSAR) Analysis ofMolecules (Basel, Switzerland) · 2021Article
- Nitroreductase-Mediated Release of Inhibitors of Lysine-Specific Demethylase 1 (LSD1) from Prodrugs in Transfected Acute Myeloid Leukaemia Cells.Chembiochem : a European journal of chemical biology · 2020Article
- Co-Prodrugs of 7-Ethyl-10-hydroxycamptothecin and Vorinostat with in Vitro Hydrolysis and Anticancer Effects.ACS omega · 2020Article
- Targeting Metalloenzymes for Therapeutic Intervention.Chemical reviews · 2019Review
- HACS medicinal chemistry letters · 2018Article
- Biocompatible Boron-Containing Prodrugs of Belinostat for the Potential Treatment of Solid Tumors.ACS medicinal chemistry letters · 2018Article
- Bifunctional conjugates with potent inhibitory activity towards cyclooxygenase and histone deacetylase.Bioorganic & medicinal chemistry · 2017Article
- Targeting Non-Catalytic Cysteine Residues Through Structure-Guided Drug Discovery.Current topics in medicinal chemistry · 2017Review
- A facile route to form self-carried redox-responsive vorinostat nanodrug for effective solid tumor therapy.International journal of nanomedicineArticle
- Epigenetic polypharmacology: from combination therapy to multitargeted drugs.Clinical epigeneticsReview
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Histone deacetylase inhibitors (HDACi) target abnormal epigenetic states associated with a variety of pathologies, including cancer. Here, the development of a prodrug of the canonical broad-spectrum HDACi suberoylanilide hydroxamic acid (SAHA) is described. Although hydroxamic acids are utilized universally in the development of metalloenzyme inhibitors, they are considered to be poor pharmacophores with reduced activity in vivo. We developed a prodrug of SAHA by appending a promoiety, sensitive to thiols, to the hydroxamic acid warhead (termed SAHA-TAP). After incubation of SAHA-TAP with an HDAC, the thiol of a conserved HDAC cysteine residue becomes covalently tagged with the promoiety, initiating a cascade reaction that leads to the release of SAHA. Mass spectrometry and enzyme kinetics experiments validate that the cysteine residue is covalently appended with the TAP promoiety. SAHA-TAP demonstrates cytotoxicity activity against various cancer cell lines. This strategy represents an original prodrug design with a dual mode of action for HDAC inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.