Discovery and Development of Potent and Selective Inhibitors of Histone Methyltransferase G9a

Overview

Journal ACS Med Chem Lett

Publisher American Chemical Society

Specialty Chemistry

Date 2014 Jun 6

PMID 24900801

Citations 73

Authors

Ramzi F Sweis

Marina Pliushchev

Peter J Brown

Jun Guo

Fengling Li

David Maag

Andrew M Petros

Nirupama B Soni

Chris Tse

Masoud Vedadi

Michael R Michaelides

Gary G Chiang

William N Pappano

Affiliations

Soon will be listed here.

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.

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