Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors

J Med Chem. 2019 Mar 14;62(5):2843-2848. doi: 10.1021/acs.jmedchem.9b00102. Epub 2019 Feb 21.

Abstract

The protein kinase MKK7 is linked to neuronal development and the onset of cancer. The field, however, lacks high-quality functional probes that would allow for the dissection of its detailed functions. Against this background, we describe an effective covalent inhibitor of MKK7 based on the pyrazolopyrimidine scaffold.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography, X-Ray
  • Drug Design
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • MAP Kinase Kinase 7 / antagonists & inhibitors*
  • Phosphorylation
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / pharmacology*
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology

Substances

  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 7
  • MAP2K7 protein, human