Advances in the discovery of selective JAK inhibitors

Prog Med Chem. 2013;52:153-223. doi: 10.1016/B978-0-444-62652-3.00004-1.


In this review, we describe the current knowledge of the biology of the JAKs. The JAK family comprises the four nonreceptor tyrosine kinases JAK1, JAK2, JAK3, and Tyk2, all key players in the signal transduction from cytokine receptors to transcription factor activation. We also review the progresses made towards the optimization of JAK inhibitors and the importance of their selectivity profile. Indeed, the full array of many medicinal chemistry enabling tools (HTS, X-ray crystallography, scaffold morphing, etc.) has been deployed to successfully design molecules that discriminate among JAK family and other kinases. While the first JAK inhibitor was launched in 2011, this review also summarizes the status of several other small-molecule JAK inhibitors currently in development to treat arthritis, psoriasis, organ rejection, and multiple cancer types.

Publication types

  • Review

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / enzymology
  • Humans
  • Janus Kinases / antagonists & inhibitors*
  • Janus Kinases / metabolism
  • Models, Molecular
  • Myeloproliferative Disorders / drug therapy*
  • Myeloproliferative Disorders / enzymology
  • Protein Kinase Inhibitors / chemistry*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use


  • Protein Kinase Inhibitors
  • Janus Kinases