Identification of the KDM2/7 histone lysine demethylase subfamily inhibitor and its antiproliferative activity.

Journal article

Histone N(ε)-methyl lysine demethylases KDM2/7 have been identified as potential targets for cancer therapies. On the basis of the crystal structure of KDM7B, we designed and prepared a series of hydroxamate analogues bearing an alkyl chain. Enzyme assays revealed that compound 9 potently inhibits KDM2A, KDM7A, and KDM7B, with IC50s of 6.8, 0.2, and 1.2 μM, respectively. While inhibitors of KDM4s did not show any effect on cancer cells tested, the KDM2/7-subfamily inhibitor 9 exerted antiproliferative activity, indicating the potential for KDM2/7 inhibitors as anticancer agents.

Authors: Suzuki, T; Ozasa, H; Itoh, Y; Zhan, P; Sawada, H

• Publication status: Published
• Journal: Journal of medicinal chemistry
• Volume: 56
• Issue: 18
• Pages: 7222-7231
• Publication date: 2013-09-01
• DOI: 10.1021/jm400624b
• EISSN: 1520-4804
• ISSN: 0022-2623
• Language: English
• Keywords: Inhibitory Concentration 50; Models, Molecular; Histone Demethylases; Cell Proliferation; Cell Line, Tumor; Enzyme Inhibitors; Drug Screening Assays, Antitumor; Antineoplastic Agents; Catalytic Domain; Humans