Medicinal chemistry updates of novel HDACs inhibitors (2020 to present)

Xingrui He; Zi Hui; Li Xu; Renren Bai; Yuan Gao; Zongcheng Wang; Tian Xie; Xiang-Yang Ye

doi:10.1016/j.ejmech.2021.113946

Medicinal chemistry updates of novel HDACs inhibitors (2020 to present)

Eur J Med Chem. 2022 Jan 5:227:113946. doi: 10.1016/j.ejmech.2021.113946. Epub 2021 Oct 22.

Authors

Xingrui He¹, Zi Hui², Li Xu², Renren Bai², Yuan Gao³, Zongcheng Wang⁴, Tian Xie⁵, Xiang-Yang Ye⁶

Affiliations

¹ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; School of Pharmacy, Liaocheng University, Shandong, 252000, China; Hunan Engineering Technology Research Center for Comprehensive Development and Utilization of Biomass Resources, Hunan University of Science and Engineering, Yongzhou, 425199, China.
² School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China.
³ Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 200000, China.
⁴ Hunan Engineering Technology Research Center for Comprehensive Development and Utilization of Biomass Resources, Hunan University of Science and Engineering, Yongzhou, 425199, China. Electronic address: wangzongch@huse.edu.cn.
⁵ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address: xbs@hznu.edu.cn.
⁶ School of Pharmacy, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China; Key Laboratory of Elemene Class Anti-Cancer Chinese Medicines, Engineering Laboratory of Development and Application of Traditional Chinese Medicines, Collaborative Innovation Center of Traditional Chinese Medicines of Zhejiang Province, Hangzhou Normal University, Hangzhou, Zhejiang, 311121, China. Electronic address: xyye@hznu.edu.cn.

PMID: 34775332
DOI: 10.1016/j.ejmech.2021.113946

Abstract

Epigentic enzymes histone deacetylases (HDACs) catalyze the removal of acetyl groups from the ε-N-acetylated lysine residues of various protein substrates including both histone and non-histone proteins. Different HDACs have distinct biological functions and are recruited to specific regions of the genome. Due to their important biological functions, HDACs have been validated in clinics for anticancer therapy, and are being explored for potential treatment of several other diseases such as Alzheimer disease (AD), metabolic disease, viral infection, and multiple sclerosis, etc. Besides five approved drugs, there are more than thirty HDACs inhibitors currently being investigated in clinical trials. Centering on the advances of drug discovery programs in this field since 2020, this review discusses HDACs inhibitors from the aspects of the structure-based rational design, isoform selectivity, pharmacology, and toxicology of the compounds of interest. The hope is to provide the medicinal chemistry community with up-to-date information and to accelerate the drug discovery programs in this area.

Keywords: Epigenetics; Histone deacetylases (HDACs); Inhibitor; Kinases.

Publication types

Review

MeSH terms

Chemistry, Pharmaceutical
Histone Deacetylase Inhibitors / chemistry
Histone Deacetylase Inhibitors / pharmacology*
Histone Deacetylases / metabolism*
Humans
Molecular Structure

Substances

Histone Deacetylase Inhibitors
Histone Deacetylases