title: Aryl Pyrazoles as Potent Inhibitors of Arginine Methyltransferases: Identification of the First PRMT6 Tool Compound.
abstract: A novel aryl pyrazole series of arginine methyltransferase inhibitors has been identified. Synthesis of analogues within this series yielded the first potent, selective, small molecule PRMT6 inhibitor tool compound, EPZ020411. PRMT6 overexpression has been reported in several cancer types suggesting that inhibition of PRMT6 activity may have therapeutic utility. Identification of EPZ020411 provides the field with the first small molecule tool compound for target validation studies. EPZ020411 shows good bioavailability following subcutaneous dosing in rats making it a suitable tool for in vivo studies.
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Lorna H
authors.initials: LH
authors.lastname: Mitchell
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Allison E
authors.initials: AE
authors.lastname: Drew
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Ribich
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Kerren K
authors.initials: KK
authors.lastname: Swinger
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Suzanne L
authors.initials: SL
authors.lastname: Jacques
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Trupti
authors.initials: T
authors.lastname: Lingaraj
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: P Ann
authors.initials: PA
authors.lastname: Boriack-Sjodin
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Nigel J
authors.initials: NJ
authors.lastname: Waters
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Tim J
authors.initials: TJ
authors.lastname: Wigle
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Oscar
authors.initials: O
authors.lastname: Moradei
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Tom
authors.initials: T
authors.lastname: Riera
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Margaret
authors.initials: M
authors.lastname: Porter-Scott
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Mikel P
authors.initials: MP
authors.lastname: Moyer
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Smith
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Richard
authors.initials: R
authors.lastname: Chesworth
authors.affiliation: Epizyme, Inc. , 400 Technology Square, Fourth Floor, Cambridge, Massachusetts 02138, United States.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Copeland
keywords: PRMT6; oncology; protein methyltransferase; tool compound