Development of JmjC-domain-containing histone demethylase (KDM2-7) inhibitors for cancer therapy

Histone methylation is the most common histone modification and a highly dynamic regulator of gene transcription. Methylation of lysine residues can alter the structure of chromatin, helping to regulate DNA-based nuclear activities. Lysine demethylases control and maintain epigenetic factors that affect chromatin structure and cell characteristics. A variety of diseases, including malignant tumors, are connected to their dysregulation. Advances in biochemistry and pathogenesis have prompted the discovery of small molecule inhibitors and tool compounds that disrupt lysine demethylation. In this review, we focus on JmjC-domain-containing histone lysine demethylases (KDM2-7), discussing their structures and biological roles, representative inhibitors, and therapeutic potential in cancer therapy, and aiming to provide unique insights into the development of JmjC-KDM inhibitors.

Automated summary

Histone methylation is a common and dynamic histone modification that regulates gene transcription by changing chromatin structure. Lysine demethylases play a vital role in maintaining epigenetic factors and are involved in various diseases, including cancer. Recent advancements have led to the discovery of inhibitors that disrupt lysine demethylation, particularly focusing on JmjC-domain-containing histone lysine demethylases (KDM2-7). This review discusses their structures, biological roles, representative inhibitors, and therapeutic potential, offering insights into the development of JmjC-KDM inhibitors.