title: Discovery and Optimization of Tetramethylpiperidinyl Benzamides as Inhibitors of EZH2.
abstract: The identification and development of a novel series of small molecule Enhancer of Zeste Homologue 2 (EZH2) inhibitors is described. A concise and modular synthesis enabled the rapid development of structure-activity relationships, which led to the identification of 44 as a potent, SAM-competitive inhibitor of EZH2 that dose-dependently decreased global H3K27me3 in KARPAS-422 lymphoma cells.
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Nasveschuk
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Gagnon
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Shivani
authors.initials: S
authors.lastname: Garapaty-Rao
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Srividya
authors.initials: S
authors.lastname: Balasubramanian
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Campbell
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Christina
authors.initials: C
authors.lastname: Lee
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Louise
authors.initials: L
authors.lastname: Bergeron
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Cummings
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Patrick
authors.initials: P
authors.lastname: Trojer
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: James E
authors.initials: JE
authors.lastname: Audia
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Brian K
authors.initials: BK
authors.lastname: Albrecht
authors.affiliation: Constellation Pharmaceuticals , 215 1st Street, Suite 200, Cambridge, Massachusetts 02142, United States.
authors.forename: Jean-Christophe P
authors.initials: JC
authors.lastname: Harmange
keywords: EZH2; KARPAS-422; PRC2; diphenylether; methyltransferase; tetramethylpiperidine