1.
J Med Chem
; 56(18): 7222-31, 2013 Sep 26.
Article
in English
| MEDLINE
| ID: mdl-23964788
ABSTRACT
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.
Subject(s)
Antineoplastic Agents/pharmacology , Enzyme Inhibitors/pharmacology , Histone Demethylases/antagonists & inhibitors , Catalytic Domain , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Histone Demethylases/chemistry , Humans , Inhibitory Concentration 50 , Models, Molecular
2.
Acta Derm Venereol
; 83(2): 155-6, 2003.
Article
in English
| MEDLINE
| ID: mdl-12735657