Discovery of a Selective and Potent Inhibitor of Mitogen-Activated Protein Kinase-Interacting Kinases 1 and 2 (MNK1/2) Utilizing Structure-Based Drug Design

  • J Med Chem. 2016 Apr 14;59(7):3034-45. doi: 10.1021/acs.jmedchem.5b01657.
Wooseok Han  1 ,  Yu Ding  1 ,  Yongjin Xu  1 ,  Keith Pfister  1 ,  Shejin Zhu  1 ,  Bob Warne  2 ,  Mike Doyle  2 ,  Mina Aikawa  2 ,  Payman Amiri  2 ,  Brent Appleton  1 ,  Darrin D Stuart  2 ,  Abdallah Fanidi  2 ,  Cynthia M Shafer  1
Affiliations
  • 1. Global Discovery Chemistry, Novartis Institutes for BioMedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
  • 2. Oncology, Novartis Institutes for BioMedical Research , 4560 Horton Street, Emeryville, California 94608, United States.
PMID: 27002243 DOI: 10.1021/acs.jmedchem.5b01657
Abstract

The discovery of a highly potent and selective small molecule inhibitor 9 for in vitro target validation of MNK1/2 Kinases is described. The aminopyrazine benzimidazole series was derived from an HTS hit and optimized by utilization of a docking model, conformation analysis, and binding pocket comparison against antitargets.

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