title: Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK).
abstract: The structure-based design and optimization of a novel series of selective PERK inhibitors are described resulting in the identification of 44 as a potent, highly selective, and orally active tool compound suitable for PERK pathway biology exploration both in vitro and in vivo.
authors.affiliation: Departments of †Medicinal Chemistry, ‡Molecular Structure and Characterization, §Oncology Research, and ∥Pharmacokinetics and Drug Metabolism, Amgen Inc. , One Amgen Center Drive, Thousand Oaks, California 91320-1799, United States.
authors.forename: Adrian L
authors.initials: AL
authors.lastname: Smith
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Andrews
authors.forename: Holger
authors.initials: H
authors.lastname: Beckmann
authors.forename: Steven F
authors.initials: SF
authors.lastname: Bellon
authors.forename: Pedro J
authors.initials: PJ
authors.lastname: Beltran
authors.forename: Shon
authors.initials: S
authors.lastname: Booker
authors.forename: Hao
authors.initials: H
authors.lastname: Chen
authors.forename: Young-Ah
authors.initials: YA
authors.lastname: Chung
authors.forename: Noel D
authors.initials: ND
authors.lastname: D'Angelo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Dao
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Dellamaggiore
authors.forename: Peter
authors.initials: P
authors.lastname: Jaeckel
authors.forename: Richard
authors.initials: R
authors.lastname: Kendall
authors.forename: Katja
authors.initials: K
authors.lastname: Labitzke
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Long
authors.forename: Silvia
authors.initials: S
authors.lastname: Materna-Reichelt
authors.forename: Petia
authors.initials: P
authors.lastname: Mitchell
authors.forename: Mark H
authors.initials: MH
authors.lastname: Norman
authors.forename: David
authors.initials: D
authors.lastname: Powers
authors.forename: Mark
authors.initials: M
authors.lastname: Rose
authors.forename: Paul L
authors.initials: PL
authors.lastname: Shaffer
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Wu
authors.forename: J Russell
authors.initials: JR
authors.lastname: Lipford
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; C460640:EIF2AK3 protein, human; D019892:eIF-2 Kinase