Cited by 189Histone Deacetylase Inhibitors ResearchEnzyme function and inhibitionCholinesterase and Neurodegenerative Diseases

Human HDAC isoform selectivity achieved via exploitation of the acetate release channel with structurally unique small molecule inhibitors

Whitehead, Lewis, Dobler, Markus R., Radetich, Branko, Zhu, Yanyi, Atadja, Peter W., Claiborne, Tavina, Grob, Jonathan E., McRiner, Andrew +9 more·2011·Bioorganic & Medicinal Chemistry

Abstract

Herein we report the discovery of a family of novel yet simple, amino-acid derived class I HDAC inhibitors that demonstrate isoform selectivity via access to the internal acetate release channel. Isoform selectivity criteria is discussed on the basis of X-ray crystallography and molecular modeling of these novel inhibitors bound to HDAC8, potentially revealing insights into the mechanism of enzymatic function through novel structural features revealed at the atomic level.

Integrity signals

Registry

Crossref · 10.1016/j.bmc.2011.06.030

Cites

45 of 45 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Benzamides face a more difficult path to the observed binding mode, with two plausible binding trajectories: via an acetyl release and disposal channel or via the hydrophobic tube, settling into a rearranged foot pocket before forming the zinc complex.

    “The benzamides face a more difficult path to the observed binding mode, with two plausible binding trajectories. The ligand could enter via an acetyl release and disposal channel (7, 24, 33, 42) or via the hydrophobic tube, settling into a rearranged foot pocket before forming the zinc complex, which locks the inhibitor in place.”
  • In HDAC8, the presence of a tryptophan limits the available space in the foot pocket.

    “In HDAC8, the presence of a tryptophan limits the available space in the foot pocket.”

    From HDACs and the epigenetic plasticity of cancer cells: target the complexity (2022) · cites this paper as Whitehead et al., 2011

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Whitehead, L., Dobler, M. R., Radetich, B., Zhu, Y., Atadja, P. W., Claiborne, T., Grob, J. E., McRiner, A., Pancost, M. R., Patnaik, A., Shao, W., Shultz, M., Tichkule, R., Tommasi, R. A., Vash, B., Wang, P., & Stams, T.
Corresponding author
Whitehead, Lewis
Venue
Bioorganic & Medicinal Chemistry
Publisher
Elsevier BV
Published
2011-08
Volume
19
Issue
15
Pages
4626-4634
ISSN
0968-0896 (ISSN-L)
OpenAlex
W2019219956
Cited by
164
References
45
Citations by year
2026: 11 · 2025: 11 · 2024: 9 · 2023: 8 · 2022: 9 · 2021: 12 · 2020: 12 · 2019: 14 · 2018: 20 · 2017: 12 · 2016: 6 · 2015: 12 · 2014: 7 · 2013: 6 · 2012: 12
FWCI
4.15
Type
journal article
Language
en
Open access
closed
Locations
  • Bioorganic & Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
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
histone deacetylase inhibitors, class I HDACs, isoform selectivity, HDAC8, small molecule inhibitors, enzyme crystal structure, inhibitor binding mechanism
MeSH terms
Amino Acids, Histone Deacetylases, Humans, Models, Molecular, Drug Design, Crystallography, X-Ray, Acetic Acid, Protein Isoforms, Histone Deacetylase Inhibitors

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review