Discovery of a Highly Selective Cell-Active Inhibitor of the Histone Lysine Demethylases KDM2/7.

ABSTRACT: Histone lysine demethylases (KDMs) are of critical importance in the epigenetic regulation of gene expression, yet there are few selective, cell-permeable inhibitors or suitable tool compounds for these enzymes. We describe the discovery of a new class of inhibitor that is highly potent towards the histone lysine demethylases KDM2A/7A. A modular synthetic approach was used to explore the chemical space and accelerate the investigation of key structure-activity relationships, leading to the development of a small molecule with around 75-fold selectivity towards KDM2A/7A versus other KDMs, as well as cellular activity at low micromolar concentrations.

SUBMITTER: Gerken PA 

PROVIDER: S-EPMC5725665 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature