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ACS Med Chem Lett. 2014 Jan 2;5(2):205-9. doi: 10.1021/ml400496h. eCollection 2014 Feb 13.

Discovery and development of potent and selective inhibitors of histone methyltransferase g9a.

Author information

1
Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
2
Structural Genomics Consortium, University of Toronto , Toronto, Canada.

Abstract

G9a is a histone lysine methyltransferase responsible for the methylation of histone H3 lysine 9. The discovery of A-366 arose from a unique diversity screening hit, which was optimized by incorporation of a propyl-pyrrolidine subunit to occupy the enzyme lysine channel. A-366 is a potent inhibitor of G9a (IC50: 3.3 nM) with greater than 1000-fold selectivity over 21 other methyltransferases.

KEYWORDS:

A-366; G9a; epigenetics; methylation; methyltransferase

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