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

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

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.

Figures
Products