JAK/STAT Signal Transduction: Promising Attractive Targets for Immune, Inflammatory and Hematopoietic Diseases

Curr Drug Targets. 2018;19(5):487-500. doi: 10.2174/1389450117666161207163054.

Abstract

Background: JAK/STAT signal pathway, a requisite part in the signaling process of growth factors and cytokines, has become attractive targets for numerous immune, inflammatory and hematopoietic diseases.

Objective: Herein, we present a review of the JAK/STAT signal pathway, the structure, biological function, mechanism of the JAKs and STATs along with a summary of the up-to-date clinical or approved JAK inhibitors which are involved in the treatment of various kinds of tumors and other immunity indications. Moreover, kinds of recently discovered JAKs inhibitors with potent activity or promising selectivity are also briefly discussed.

Conclusion: Research and development of isoform selective JAK inhibitors has become a hot topic in this field. With the assistance of high throughput screening and rational drug design, more and more JAK inhibitors with improved selective profiles will be discovered as biological probes and even therapeutic agents.

Keywords: Inflammation; JAK; STAT; kinase inhibitors; selectivity; signal transduction.

Publication types

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

MeSH terms

  • Animals
  • Clinical Trials as Topic
  • Hematologic Diseases / drug therapy
  • Hematologic Diseases / metabolism*
  • Humans
  • Immune System Diseases / drug therapy
  • Immune System Diseases / metabolism*
  • Inflammation / drug therapy
  • Inflammation / metabolism*
  • Janus Kinases / chemistry
  • Janus Kinases / metabolism
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • STAT Transcription Factors / chemistry
  • STAT Transcription Factors / metabolism
  • Signal Transduction / drug effects*

Substances

  • Protein Kinase Inhibitors
  • STAT Transcription Factors
  • Janus Kinases