High-throughput screening to identify inhibitors of lysine demethylases

Abstract

Lysine demethylases (KDMs) are epigenetic regulators whose dysfunction is implicated in the pathology of many human diseases including various types of cancer, inflammation and X-linked intellectual disability. Particular demethylases have been identified as promising therapeutic targets, and tremendous efforts are being devoted toward developing suitable small-molecule inhibitors for clinical and research use. Several High-throughput screening strategies have been developed to screen for small-molecule inhibitors of KDMs, each with advantages and disadvantages in terms of time, cost, effort, reliability and sensitivity. In this Special Report, we review and evaluate the High-throughput screening methods utilized for discovery of novel small-molecule KDM inhibitors.

Keywords::

• High-throughput screening
• JmjC
• KDM
• lysine demethylase
• LSD1
• small-molecule inhibitor

Financial & competing interests disclosure

This work was supported by American Cancer Society Research Scholar Grant RSG-13-384-01-DMC, Connecticut Department of Public Health Biomedical Research Grant 2013-0201, Department of Defense Peer Reviewed Cancer Research Program Career Development Award W81XWH-13-1-0235 and Department of Defense Breast Cancer Research Program Breakthrough Award W81XWH-14-1-0308 to Q Yan, and NIH grant CA16359 (to the Yale Comprehensive Cancer Center). M Gale is supported by NSF Graduate Research Fellowship DGE-1122492. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This work was supported by American Cancer Society Research Scholar Grant RSG-13-384-01-DMC, Connecticut Department of Public Health Biomedical Research Grant 2013-0201, Department of Defense Peer Reviewed Cancer Research Program Career Development Award W81XWH-13-1-0235 and Department of Defense Breast Cancer Research Program Breakthrough Award W81XWH-14-1-0308 to Q Yan, and NIH grant CA16359 (to the Yale Comprehensive Cancer Center). M Gale is supported by NSF Graduate Research Fellowship DGE-1122492. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.