Targeting SOCS Proteins to Control JAK-STAT Signalling in Disease

Trends Pharmacol Sci. 2019 May;40(5):298-308. doi: 10.1016/ Epub 2019 Apr 2.


Defective regulation of the Janus kinase-signal transducer and activator of transcription (JAK-STAT) signalling pathway in cancers, haematological diseases, and chronic inflammatory conditions highlights its clinical significance. While several biologic and small molecule therapeutics targeting this pathway have been developed, these have several limitations. Therefore, there is a need to identify new targets for intervention. Suppressor of cytokine signalling (SOCS) proteins are a family of inducible inhibitors of cytokine receptors that activate the JAK-STAT pathway. Here we propose that newly identified mechanisms controlling SOCS function could be exploited to develop molecularly targeted drugs with unique modes of action to inhibit JAK-STAT signalling in disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Janus Kinases / antagonists & inhibitors
  • Janus Kinases / metabolism*
  • Molecular Targeted Therapy
  • STAT Transcription Factors / antagonists & inhibitors
  • STAT Transcription Factors / metabolism*
  • Signal Transduction / drug effects*
  • Small Molecule Libraries / pharmacology
  • Suppressor of Cytokine Signaling Proteins / antagonists & inhibitors
  • Suppressor of Cytokine Signaling Proteins / metabolism*


  • STAT Transcription Factors
  • Small Molecule Libraries
  • Suppressor of Cytokine Signaling Proteins
  • Janus Kinases