Characterization of FGF401 as a reversible covalent inhibitor of fibroblast growth factor receptor 4

Chem Commun (Camb). 2019 May 21;55(42):5890-5893. doi: 10.1039/c9cc02052g.

Abstract

Biochemical and structural studies provide information on the mode of action of FGF401 as a selective, reversible covalent inhibitor of FGFR4. Kinase and proliferation assays reveal that FGF401 has the ability to overcome gatekeeper mutations in FGFR4.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Transformed
  • Cell Proliferation / drug effects
  • Humans
  • Inhibitory Concentration 50
  • Mass Spectrometry
  • Mutation
  • Piperazines / pharmacology*
  • Protein Kinase Inhibitors / pharmacology
  • Pyridines / pharmacology*
  • Receptor, Fibroblast Growth Factor, Type 4 / antagonists & inhibitors*
  • Receptor, Fibroblast Growth Factor, Type 4 / chemistry
  • Receptor, Fibroblast Growth Factor, Type 4 / genetics
  • Sequence Homology, Amino Acid

Substances

  • Piperazines
  • Protein Kinase Inhibitors
  • Pyridines
  • FGFR4 protein, human
  • Receptor, Fibroblast Growth Factor, Type 4
  • roblitinib