HDAC8 as an emerging target in drug discovery with special emphasis on medicinal chemistry

HDAC8 catalyzes the deacetylation of both histones and nonhistone proteins. The abnormal expression of HDAC8 is associated with various pathological conditions causing cancer and other diseases like myopathies, Cornelia de Lange syndrome, renal fibrosis, and viral and parasitic infections. The substrates of HDAC8 are involved in diverse molecular mechanisms of cancer such as cell proliferation, invasion, metastasis and drug resistance. Based on the crystal structures and the key residues at the active site, HDAC8 inhibitors have been designed along the canonical pharmacophore. This article details the importance, recent advancements, and the structural and functional aspects of HDAC8 with special emphasis on the medicinal chemistry aspect of HDAC8 inhibitors that will help in developing novel epigenetic therapeutics.

Automated summary

HDAC8 is responsible for removing acetyl groups from both histones and nonhistone proteins. Abnormal expression of HDAC8 is associated with various diseases, including cancer, myopathies, Cornelia de Lange syndrome, renal fibrosis, and viral and parasitic infections. HDAC8 substrates play important roles in cancer-related processes such as cell proliferation, invasion, metastasis, and drug resistance. This article focuses on the importance, recent advancements, and the structural and functional aspects of HDAC8, with a special emphasis on the medicinal chemistry of HDAC8 inhibitors for the development of novel epigenetic therapeutics.