Recent Progress in Histone Demethylase Inhibitors.

Area of Science:

• Biochemistry
• Molecular Biology
• Medicinal Chemistry

Background:

• Histone N-methyl-lysine demethylases (KDMs) are epigenetic regulators increasingly targeted by small molecules.
• KDMs play roles in various biological processes and diseases, making them attractive therapeutic targets.
• Previous reviews have summarized KDM inhibitor development, necessitating an update.

Purpose of the Study:

• To provide a comprehensive update on the inhibition of lysine-specific demethylases (LSDs or KDM1s) and JmjC families of N-methyl-lysine demethylases (JmjC KDMs, KDM2-7).
• To focus on academic and patent literature published from 2014 to the present.
• To highlight recent biochemical, biological, and structural studies relevant to KDM inhibitor development.

Main Methods:

• Literature review of academic publications and patents from 2014 to date.
• Analysis of biochemical, biological, and structural studies related to KDM inhibitors.
• Synthesis of information on KDM inhibitor development strategies.

Main Results:

• Significant advancements in the development of small molecule inhibitors for various KDM families.
• Identification of key structural features and biochemical mechanisms underlying KDM inhibition.
• Emerging biological applications and therapeutic potential of KDM inhibitors.

Conclusions:

• Small molecule inhibitors targeting KDMs represent a promising area for both chemical probe development and therapeutic intervention.
• Continued research into KDM biology and inhibitor design is crucial for advancing epigenetic therapies.
• The reviewed literature provides a valuable resource for researchers in the field of KDM inhibitor development.