Structure-based drug design enables conversion of a DFG-in binding CSF-1R kinase inhibitor to a DFG-out binding mode

Bioorg Med Chem Lett. 2010 Mar 1;20(5):1543-7. doi: 10.1016/j.bmcl.2010.01.078. Epub 2010 Jan 21.


The work described herein demonstrates the utility of structure-based drug design (SBDD) in shifting the binding mode of an HTS hit from a DFG-in to a DFG-out binding mode resulting in a class of novel potent CSF-1R kinase inhibitors suitable for lead development.

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Drug Design
  • High-Throughput Screening Assays
  • Hydrogen Bonding
  • Molecular Conformation
  • Protein Binding
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology
  • Receptor, Macrophage Colony-Stimulating Factor / antagonists & inhibitors*
  • Receptor, Macrophage Colony-Stimulating Factor / metabolism


  • Protein Kinase Inhibitors
  • Receptor, Macrophage Colony-Stimulating Factor