Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications
Summary
Type I/II cytokine receptors mediate cytokine-specific biological responses by employing a defined combination of four Janus kinases (JAKs) and seven signal transducers and activators of transcription (STATs) for cellular signal transduction. Deregulation of the JAK-STAT pathway leads to various diseases, with JAK and STAT proteins representing attractive therapeutic targets. Fifteen JAK inhibitors are approved for several immunological and haematological diseases, offering significant ben
Content
# Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications
*Published: 2026 Apr*
Type I/II cytokine receptors mediate cytokine-specific biological responses by
employing a defined combination of four Janus kinases (JAKs) and seven signal
transducers and activators of transcription (STATs) for cellular signal
transduction. Deregulation of the JAK-STAT pathway leads to various diseases,
with JAK and STAT proteins representing attractive therapeutic targets. Fifteen
JAK inhibitors are approved for several immunological and haematological
diseases, offering significant benefits for patients. However, safety
restrictions have limited their clinical use. Mechanistic and structural
insights are driving current drug development approaches focused on improving
their potency, selectivity and safety. Development of STAT inhibitors has been
more challenging, and none has yet received clinical approval, although
promising new compounds are now entering clinical trials. This Review discusses
the recent advances in JAK and STAT inhibitor development and presents emerging
therapeutic indications for JAK-STAT inhibition.
DOI: 10.1038/s41573-025-01336-9