Benesch JLP

Brennan PE

Chandler SA

Fedorov O

Gerken PA

Hatch SB

Kawamura A

Kessler BM

Konietzny R

Li F

Mair B

Muller S

Nijman SMB

Smith MD

Szommer T

Tumber A

Vedadi M

Wolstenhulme JR

Yapp C

Zhang Y

\ua9 2017 The Authors. Published by Wiley-VCH Verlag GmbH &amp; Co. KGaA. 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

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

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

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