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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

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

Sweis Ramzi F RF Pliushchev Marina M Brown Peter J PJ Guo Jun J Li Fengling F Maag David D Petros Andrew M AM Soni Nirupama B NB Tse Chris C Vedadi Masoud M Michaelides Michael R MR Chiang Gary G GG Pappano William N WN

ACS medicinal chemistry letters 20140102 2

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. ...[more]

PMID: 24900801

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