Magic bullets for protein kinases

Trends Cell Biol. 2001 Apr;11(4):167-72. doi: 10.1016/s0962-8924(01)01928-6.


A chemical-genetic method for the generation of target-specific protein kinase inhibitors has been developed recently. This strategy utilizes a functionally silent active-site mutation to sensitize a target kinase to inhibition by a small molecule that does not inhibit wild-type kinases. Tyrosine and serine/threonine kinases are equally amenable to the drug-sensitization approach, which has been used to generate selective inhibitors of mutant Src-family kinases, Abl-family kinases, cyclin-dependent kinases, mitogen-activated kinases, p21-activated kinases and Ca(2+)/calmodulin-dependent kinases. The designed inhibitors are specific for the sensitized kinase in a cellular background where the wild-type kinase has been inactivated. By these means, kinase-sensitization has been used systematically to generate and analyze conditional alleles of several yeast protein kinases in vivo.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / chemical synthesis*
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism
  • Drug Delivery Systems / methods
  • Drug Delivery Systems / trends
  • Drug Design
  • Genetic Therapy / methods
  • Genetic Therapy / trends
  • Humans
  • Intracellular Signaling Peptides and Proteins*
  • Mutagenesis
  • Protein Kinases / drug effects
  • Protein Kinases / genetics*
  • Protein Kinases / therapeutic use*


  • Carrier Proteins
  • Intracellular Signaling Peptides and Proteins
  • protein kinase modulator
  • Protein Kinases