Potent and selective small molecule inhibitors of specific isoforms of Cdc2-like kinases (Clk) and dual specificity tyrosine-phosphorylation-regulated kinases (Dyrk).

Medicinal Chemistry
Profiling

Abstract

Continued examination of substituted 6-arylquinazolin-4-amines as Clk4 inhibitors resulted in selective inhibitors of Clk1, Clk4, Dyrk1A and Dyrk1B. Several of the most potent inhibitors were validated as being highly selective within a comprehensive kinome scan.

Authors

Rosenthal, Andrew S; Tanega, Cordelle; Shen, Min; Mott, Bryan T; Bougie, James M; Nguyen, Trung; Misteli, Tom; Auld, Douglas S; Maloney, David J; Thomas, Craig;

Keywords

  • Enzyme Activation/ drug effects
  • Enzyme Inhibitors/ chemical synthesis
  • Enzyme Inhibitors/ chemistry
  • Enzyme Inhibitors/ pharmacology
  • Inhibitory Concentration 50
  • Isoenzymes/ antagonists & inhibitors
  • Models, Molecular
  • Molecular Structure
  • Phosphorylation
  • Protein-Serine-Threonine Kinases/ antagonists & inhibitors
  • Protein-Serine-Threonine Kinases/ metabolism
  • Protein-Tyrosine Kinases/ antagonists & inhibitors
  • Protein-Tyrosine Kinases/ metabolism
  • Quinazolines/ chemical synthesis
  • Quinazolines/ chemistry
  • Quinazolines/ pharmacology
  • Small Molecule Libraries/ chemical synthesis
  • Small Molecule Libraries/ chemistry
  • Small Molecule Libraries/ pharmacology
  • Substrate Specificity
  • Thiazoles/ chemical synthesis
  • Thiazoles/ chemistry
  • Thiazoles/ pharmacology

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