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.
Mark Zak  1 ,  Hart S Dengler  2 ,  Naomi S Rajapaksa  3
Affiliations
  • 1. Genentech Inc., Discovery Chemistry, 1 DNA Way, South San Francisco, CA 94080, USA. Electronic address: [email protected].
  • 2. Genentech Inc., Immunology Department, 1 DNA Way, South San Francisco, CA 94080, USA.
  • 3. Genentech Inc., Discovery Chemistry, 1 DNA Way, South San Francisco, CA 94080, USA.
PMID: 31522830 DOI: 10.1016/j.bmcl.2019.126658
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.
Products