ArticleACS medicinal chemistry letters2012
Discovery of HDAC Inhibitors That Lack an Active Site Zn(2+)-Binding Functional Group.
Article in ACS medicinal chemistry letters, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Chromatin Regulatory Targets for Anticancer Therapeutics.Chemical reviews · 2025Review
- Design, synthesis, biological andBiomedical reports · 2025Article
- Control of metalloenzyme activity using photopharmacophores.Coordination chemistry reviews · 2024Article
- Discovery of a Novel and Potent Dual-Targeting Inhibitor of ATM and HDAC2 Through Structure-Based Virtual Screening for the Treatment of Testicular Cancer.Drug design, development and therapy · 2024Article
- Phage-assisted, active site-directed ligand evolution of a potent and selective histone deacetylase 8 inhibitor.Protein science : a publication of the Protein Society · 2022Article
- Design, synthesis, and cytotoxicity evaluation of novel indole-acylhydrazone derivatives of 4-pyridinone as potential histone deacetylase-2 inhibitors.Research in pharmaceutical sciences · 2022Article
- Cyclic Tetrapeptide HDAC Inhibitors with ImprovedACS infectious diseases · 2021Article
- Redefining the Histone Deacetylase Inhibitor Pharmacophore: High Potency with No Zinc Cofactor Interaction.ACS medicinal chemistry letters · 2021Article
- Novel Histone Deacetylase Inhibitors and HIV-1 Latency-Reversing Agents Identified by Large-Scale Virtual Screening.Frontiers in pharmacology · 2020Article
- Review
- α,ß-Didehydrosuberoylanilide hydroxamic acid (DDSAHA) as precursor and possible analogue of the anticancer drug SAHA.Beilstein journal of organic chemistry · 2019Article
- Hydroxyl Ketone-Based Histone Deacetylase Inhibitors To Gain Insight into Class I HDAC Selectivity versus That of HDAC6.ACS omega · 2017Article
- The effect of metalloprotein inhibitors on cellular metal ion content and distribution.Metallomics : integrated biometal science · 2017Article
- Structural Requirements of HDAC Inhibitors: SAHA Analogues Modified at the C2 Position Display HDAC6/8 Selectivity.ACS medicinal chemistry letters · 2017Article
- Development of Allosteric Hydrazide-Containing Class I Histone Deacetylase Inhibitors for Use in Acute Myeloid Leukemia.Journal of medicinal chemistry · 2016Article
- Natural compound-derived epigenetic regulators targeting epigenetic readers, writers and erasers.Current topics in medicinal chemistry · 2016Review
- Investigating the Selectivity of Metalloenzyme Inhibitors in the Presence of Competing Metalloproteins.ChemMedChem · 2015Article
- Targeting the histone orthography of cancer: drugs for writers, erasers and readers.British journal of pharmacology · 2015Review
- Microbial natural products: molecular blueprints for antitumor drugs.Journal of industrial microbiology & biotechnology · 2013Review
- Investigating the selectivity of metalloenzyme inhibitors.Journal of medicinal chemistry · 2013Article
Corrections and comments
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Authors and funding
4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Natural and synthetic histone deacetylase (HDAC) inhibitors generally derive their strong binding affinity and high potency from a key functional group that binds to the Zn(2+) ion within the enzyme active site. However, this feature is also thought to carry the potential liability of undesirable off-target interactions with other metalloenzymes. As a step toward mitigating this issue, here, we describe the design, synthesis, and structure-activity characterizations of cyclic α3β-tetrapeptide HDAC inhibitors that lack the presumed indispensable Zn(2+)-binding group. The lead compounds (e.g., 15 and 26) display good potency against class 1 HDACs and are active in tissue culture against various human cancer cell lines. Importantly, enzymological analysis of 26 indicates that the cyclic α3β-tetrapeptide is a fast-on/off competitive inhibitor of HDACs 1-3 with K i values of 49, 33, and 37 nM, respectively. Our proof of principle study supports the idea that novel classes of HDAC inhibitors, which interact at the active-site opening, but not with the active site Zn(2+), can have potential in drug design.
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