Inhaled Janus Kinase (JAK) inhibitors for the treatment of asthma

Bioorg Med Chem Lett. 2019 Oct 15;29(20):126658. doi: 10.1016/j.bmcl.2019.126658. Epub 2019 Sep 3.

Abstract

Multiple asthma-relevant cytokines including IL-4, IL-5, IL-13, and TSLP depend upon JAKs for signaling. JAK inhibition may, therefore, offer a novel intervention strategy for patients with disease refractory to current standards of care. Multiple systemically delivered JAK inhibitors have been approved for human use or are under clinical evaluation in autoimmune diseases such as rheumatoid arthritis. However, the on-target side effect profiles of these agents are likely not tolerable for many asthmatic patients. Limiting JAK inhibition to the lung is expected to improve therapeutic index relative to systemic inhibition. Thus, inhaled JAK inhibitors with lung-restricted exposure are of high interest as potential treatments for asthma.

Keywords: Asthma; Cytokine; Immunology; Inhalation; JAK; Janus Kinase; Kinase inhibitor; Lung-targeted; Respiratory.

Publication types

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

MeSH terms

  • Administration, Inhalation
  • Animals
  • Asthma / metabolism*
  • Autoimmune Diseases / drug therapy*
  • Cytokines / metabolism
  • Drug Compounding
  • Drug Liberation
  • Humans
  • Janus Kinase Inhibitors / administration & dosage*
  • Janus Kinase Inhibitors / adverse effects
  • Janus Kinase Inhibitors / therapeutic use
  • Janus Kinases / antagonists & inhibitors*
  • Lung / drug effects
  • Molecular Structure
  • Phosphorylation
  • Signal Transduction
  • Treatment Outcome

Substances

  • Cytokines
  • Janus Kinase Inhibitors
  • Janus Kinases