title: 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.
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Ramzi F
authors.initials: RF
authors.lastname: Sweis
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Marina
authors.initials: M
authors.lastname: Pliushchev
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Canada.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Brown
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Guo
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Canada.
authors.forename: Fengling
authors.initials: F
authors.lastname: Li
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: David
authors.initials: D
authors.lastname: Maag
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Petros
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Nirupama B
authors.initials: NB
authors.lastname: Soni
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Tse
authors.affiliation: Structural Genomics Consortium, University of Toronto , Toronto, Canada.
authors.forename: Masoud
authors.initials: M
authors.lastname: Vedadi
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Michaelides
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: Gary G
authors.initials: GG
authors.lastname: Chiang
authors.affiliation: Discovery Research, AbbVie Inc. , 1 North Waukegan Road, North Chicago, Illinois 60064, United States.
authors.forename: William N
authors.initials: WN
authors.lastname: Pappano
keywords: A-366; G9a; epigenetics; methylation; methyltransferase