2. Academic Validation
  3. Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK)

Discovery of 1H-pyrazol-3(2H)-ones as potent and selective inhibitors of protein kinase R-like endoplasmic reticulum kinase (PERK)

  • J Med Chem. 2015 Feb 12;58(3):1426-41. doi: 10.1021/jm5017494.
Adrian L Smith 1,  Kristin L Andrews,  Holger Beckmann,  Steven F Bellon,  Pedro J Beltran,  Shon Booker,  Hao Chen,  Young-Ah Chung,  Noel D D'Angelo,  Jennifer Dao,  Kenneth R Dellamaggiore,  Peter Jaeckel,  Richard Kendall,  Katja Labitzke,  Alexander M Long,  Silvia Materna-Reichelt,  Petia Mitchell,  Mark H Norman,  David Powers,  Mark Rose,  Paul L Shaffer,  Michelle M Wu,  J Russell Lipford
Affiliations

Affiliation

  • 1 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.
PMID: 25587754 DOI: 10.1021/jm5017494
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.

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