Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2020 Jan;17(1):e1900427.
doi: 10.1002/cbdv.201900427. Epub 2019 Dec 23.

The Development Process: from SAHA to Hydroxamate HDAC Inhibitors with Branched CAP Region and Linear Linker

Feifei Yang  1 , Na Zhao  1 , Yunjie Hu  2 , Cheng-Shi Jiang  1 , Hua Zhang  1
Affiliations
Review

The Development Process: from SAHA to Hydroxamate HDAC Inhibitors with Branched CAP Region and Linear Linker

Feifei Yang et al. Chem Biodivers. 2020 Jan.

Abstract

Histone deacetylases (HDACs) belong to a group of epigenetic regulatory enzymes that participate in modulating the acetylation level of histone lysine residues as well as non-histone proteins, and they play a key role in the regulation of gene expression. HDACs are potential anticancer drug targets highly expressed in various kinds of cancer cells. So far, five small molecules targeting HDACs have been approved for the therapy of cancer, and over 20 inhibitors of HDACs are under different phases of clinical trials. Among them, hydroxamate-based HDAC inhibitors (HDACis) represent a well-investigated series of chemical entities. The current review covers the recent progress in the discovery process, form SAHA to hydroxamate HDAC inhibitors with branched CAP region and linear linker. At the same time, the pharmacological and structure-activity relationship (SAR) studies of the specific derivatives from SAHA and the HDACis with branched CAP region and linear linker are also introduced.

Keywords: CAP; cancer; histone deacetylases; hydroxamic acid; inhibitors.

PubMed Disclaimer

References

    1. C. Zwergel, S. Valente, C. Jacob, A. Mai, ‘Emerging approaches for histone deacetylase inhibitor drug discovery’, Expert Opin. Drug Discovery 2015, 10, 599-613.
    1. P. Filippakopoulos, S. Knapp, ‘Targeting bromodomains: epigenetic readers of lysine acetylation’, Nat. Rev. Drug Discovery 2014, 13, 339-356.
    1. C. Zagni, G. Floresta, G. Monciino, A. Rescifina, ‘The Search for Potent, Small-Molecule HDACIs in Cancer Treatment: A Decade After Vorinostat’, Med. Res. Rev. 2017, 37, 1373-1428.
    1. T. Harada, T. Hideshima, K. C. Anderson, ‘Histone deacetylase inhibitors in multiple myeloma: from bench to bedside’, Int. J. Hematol. 2016, 104, 300-309.
    1. M. Manal, M. J. N. Chandrasekar, J. G. Priya, M. J. Nanjan, ‘Inhibitors of histone deacetylase as antitumor agents: A critical review’, Bioorg. Chem. 2016, 67, 18-42.

MeSH terms

LinkOut - more resources