A patent review of KDM4 histone demethylase inhibitors (2014-present)

Significant progress has been achieved in the development of KDM4 inhibitors; however, most current compounds continue to face major challenges, including poor membrane permeability, limited cellular potency, and low isoform specificity. Strategies such as designing inhibitors with novel scaffolds, developing covalent inhibitors, advancing protein degraders, and targeting non-catalytic domains may provide viable solutions to these limitations. In addition, the physiological and pathological roles of KDM4 remain insufficiently characterized. Further in-depth investigations into the biological functions of KDM4 will be essential to guide the rational design and facilitate the clinical translation of KDM4-targeted therapeutics.