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Cited by 240Histone Deacetylase Inhibitors ResearchEnzyme function and inhibitionCholinesterase and Neurodegenerative Diseases

Zinc binding groups for histone deacetylase inhibitors

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Zhang, Lei, Zhang, Jian, Jiang, Qixiao, Zhang, Li, Song, Weiguo·2018·Journal of Enzyme Inhibition and Medicinal Chemistry
DOI 10.1080/14756366.2017.1417274PMC PMC6009916
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Abstract

Zinc binding groups (ZBGs) play a crucial role in targeting histone deacetylase inhibitors (HDACIs) to the active site of histone deacetylases (HDACs), thus determining the potency of HDACIs. Due to the high affinity to the zinc ion, hydroxamic acid is the most commonly used ZBG in the structure of HDACs. An alternative ZBG is benzamide group, which features excellent inhibitory selectivity for class I HDACs. Various ZBGs have been designed and tested to improve the activity and selectivity of HDACIs, and to overcome the pharmacokinetic limitations of current HDACIs. Herein, different kinds of ZBGs are reviewed and their features have been discussed for further design of HDACIs.

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  • Existing benzamide scaffold drugs inhibit class-I HDAC enzymes and are approximately equipotent for HDAC1, HDAC2, and HDAC3 in a biochemical deacetylation assay.

    “Existing drugs with a benzamide scaffold inhibit class-I HDAC enzymes, such as entinostat, mocetinostat, and tucidinostat (Fig. 2A; ref. 15). These drugs are approximately equipotent for HDAC1, HDAC2, and HDAC3 in a biochemical deacetylation assay (Supplementary Fig. S3A).”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [15]

  • Benzamide inhibitors like entinostat are selective for class-I HDACs, which include HDAC1 to HDAC3 and HDAC8.

    “Benzamide inhibitors like entinostat are selective for class-I HDACs, which include HDAC1 to HDAC3 and HDAC8 (14–16).”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [15]

  • Class-I HDAC enzymes participate in large multiprotein corepressor complexes, including the HDAC1/2 complexes CoREST, NuRD, MiDAC, and Sin3, and the HDAC3-containing complex NCoR.

    “Class-I HDAC enzymes participate in large, multiprotein corepressor complexes (14, 15), including the HDAC1/2 complexes CoREST, NuRD, MiDAC, and Sin3, and the HDAC3-containing complex NCoR (14, 17).”

    From TNG260 Is a Small-Molecule CoREST Inhibitor That Sensitizes <i>STK11</i> -Mutant Tumors to Anti–PD-1 Immunotherapy (2025) · cites this paper as [15]

    The Introduction identifies HDAC1, HDAC2, and HDAC3 as class-I enzymes, but does not describe their participation in multiprotein corepressor complexes. Searches for CoREST, NuRD, MiDAC, Sin3, NCoR, and HDAC corepressor complexes found no passage addressing the attributed relationships. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Zhang, L., Zhang, J., Jiang, Q., Zhang, L., & Song, W.
Affiliations
  • Qingdao University (CN)
  • Weifang Medical University (CN)
Corresponding author
  • Zhang, Lei
  • Song, Weiguo
ORCID
Venue
Journal of Enzyme Inhibition and Medicinal Chemistry
Publisher
Informa UK Limited
Published
2018-01-01
Volume
33
Issue
1
Pages
714-721
ISSN
  • 1475-6366 (ISSN-L)
  • 1475-6374
DOI
10.1080/14756366.2017.1417274
PMC
PMC6009916
OpenAlex
W2795615449
Cited by
240
References
2
Citations by year
2026: 14 · 2025: 32 · 2024: 34 · 2023: 40 · 2022: 35 · 2021: 36 · 2020: 30 · 2019: 15 · 2018: 3
FWCI
2.11
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Enzyme Inhibition and Medicinal Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Histone Deacetylase Inhibitors Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Enzyme function and inhibition
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
zinc-binding groups, histone deacetylase inhibitors, histone deacetylase, hydroxamic acids, benzamide, class I HDACs
MeSH terms
Histone Deacetylases, Humans, Hydroxamic Acids, Structure-Activity Relationship, Zinc, Histone Deacetylase Inhibitors

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