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

Epigentic enzymes histone deacetylases (HDACs) catalyze the removal of acetyl groups from the epsilon-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. (c) 2021 Elsevier Masson SAS. All rights reserved.

Automated summary

Histone deacetylases (HDACs) are important enzymes involved in the removal of acetyl groups from lysine residues, and have shown potential therapeutic applications in cancer and various diseases. There are currently numerous HDAC inhibitors under clinical investigation, aiming to provide up-to-date information for drug discovery programs.