2. Academic Validation
  3. Discovery and development of potent and selective inhibitors of histone methyltransferase g9a

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

  • ACS Med Chem Lett. 2014 Jan 2;5(2):205-9. doi: 10.1021/ml400496h.
Ramzi F Sweis 1,  Marina Pliushchev 1,  Peter J Brown 2,  Jun Guo 1,  Fengling Li 2,  David Maag 1,  Andrew M Petros 1,  Nirupama B Soni 1,  Chris Tse 1,  Masoud Vedadi 2,  Michael R Michaelides 1,  Gary G Chiang 1,  William N Pappano 1
Affiliations

Affiliations

  • 1 Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
  • 2 Structural Genomics Consortium, University of Toronto , Toronto, Canada.
PMID: 24900801 DOI: 10.1021/ml400496h
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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