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

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.

SUBMITTER: Sweis RF 

PROVIDER: S-EPMC4027767 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature