Targeting Epigenetic Regulatory Enzymes for Cancer Therapeutics: Novel Small-Molecule Epidrug Development

Abstract

Dysregulation of the epigenetic enzyme-mediated transcription of oncogenes or tumor suppressor genes is closely associated with the occurrence, progression, and prognosis of tumors. Based on the reversibility of epigenetic mechanisms, small-molecule compounds that target epigenetic regulation have become promising therapeutics. These compounds target epigenetic regulatory enzymes, including DNA methylases, histone modifiers (methylation and acetylation), enzymes that specifically recognize post-translational modifications, chromatin-remodeling enzymes, and post-transcriptional regulators. Few compounds have been used in clinical trials and exhibit certain therapeutic effects. Herein, we summarize the classification and therapeutic roles of compounds that target epigenetic regulatory enzymes in cancer treatment. Finally, we highlight how the natural compounds berberine and ginsenosides can target epigenetic regulatory enzymes to treat cancer.

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

“…Notably, because epigenetic alterations do not alter DNA sequences, it may be possible to "reset" the epigenome to restore cellular and tissue function and viability. 17,18 Furthermore, epigenetic changes can alter signaling pathways that regulate bone homeostasis. The present article reviews the epigenetic alterations that affect BMSC differentiation and metabolic activity in aging individuals (Figure 1).…”

The Impact of Fluorination on the Design of Histone Deacetylase Inhibitors

“…However, some HDACis have already been approved by the United States Food and Drug Administration (FDA) for the treatment of various types of cancer. Some examples include the cyclic peptide romidepsin, and the hydroxamates vorinostat (also known as SAHA—suberoylanilide hydroxamic acid), belinostat, and panobinostat ( Figure 1 ) [ 11 ]. In addition, some interesting synergistic properties were also discovered when HDACis were combined with established anticancer drugs [ 12 ].…”

Epigenetic reprogramming in cancer: From diagnosis to treatment

“…The epigenomic´s reprogramming, leading to changes in the cell landscape, reveals a promising therapeutical approach ( Miranda Furtado et al, 2019 ). Many small molecules targeting epigenetic key enzymes, called epigenetic drugs or epidrugs ( Table 1 ), have been discovered and new compounds that modulate epigenetic marks ( Figure 2 ) are being developed focusing on cancer treatment ( Xiao et al, 2021 ) ( Jin et al, 2022b ). Epidrugs promotes disruption of transcriptional and post-transcriptional modifications, acting manly on tumor suppressor and DNA repair gene activation ( Rodríguez-Paredes and Esteller, 2011 ; Ghasemi, 2020 ).…”