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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.Amodular 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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1002/anie.201706788

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
Medical Sciences Division
Department:
NDM; Target Discovery Institute
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS Division
Department:
Chemistry; Organic Chemistry
Role:
Author



Publisher:
Wiley
Journal:
Angewandte Chemie International Edition More from this journal
Publication date:
2017-11-07
Acceptance date:
2017-10-04
DOI:
EISSN:
1521-3773
ISSN:
1433-7851


Keywords:
Pubs id:
pubs:809869
UUID:
uuid:db0e3705-824b-4816-9939-b01811859716
Local pid:
pubs:809869
Source identifiers:
809869
Deposit date:
2017-12-19

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