Kinase drug discovery 20 years after imatinib: progress and future directions

Nat Rev Drug Discov. 2021 Jul;20(7):551-569. doi: 10.1038/s41573-021-00195-4. Epub 2021 May 17.


Protein kinases regulate nearly all aspects of cell life, and alterations in their expression, or mutations in their genes, cause cancer and other diseases. Here, we review the remarkable progress made over the past 20 years in improving the potency and specificity of small-molecule inhibitors of protein and lipid kinases, resulting in the approval of more than 70 new drugs since imatinib was approved in 2001. These compounds have had a significant impact on the way in which we now treat cancers and non-cancerous conditions. We discuss how the challenge of drug resistance to kinase inhibitors is being met and the future of kinase drug discovery.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Drug Delivery Systems
  • Drug Discovery / trends*
  • Drug Resistance, Neoplasm
  • Humans
  • Imatinib Mesylate / pharmacology
  • Imatinib Mesylate / therapeutic use*
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Imatinib Mesylate