Cathepsin C inhibitors as anti-inflammatory drug discovery: Challenges and opportunities

Eur J Med Chem. 2021 Dec 5:225:113818. doi: 10.1016/j.ejmech.2021.113818. Epub 2021 Sep 3.

Abstract

Cathepsin C, an important lysosomal cysteine protease, mediates the maturation process of neutrophil serine proteases, and participates in the inflammation and immune regulation process associated with polymorphonuclear neutrophils. Therefore, cathepsin C is considered to be an attractive target for treating inflammatory diseases. With INS1007 (trade name: brensocatib) being granted a breakthrough drug designation by FDA for the treatment of Adult Non-cystic Fibrosis Bronchiectasis and Coronavirus Disease 2019, the development of cathepsin C inhibitor will attract attentions from medicinal chemists in the future soon. Here, we summarized the research results of cathepsin C as a therapeutic target, focusing on the development of cathepsin C inhibitor, and provided guidance and reference opinions for the upcoming development boom of cathepsin C inhibitor.

Keywords: Cat C inhibitor; Cathepsin C; Inflammatory disease; Therapeutic target.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents / chemistry*
  • Anti-Inflammatory Agents / therapeutic use
  • COVID-19 / pathology
  • COVID-19 / virology
  • COVID-19 Drug Treatment
  • Cathepsin C / antagonists & inhibitors*
  • Cathepsin C / genetics
  • Cathepsin C / metabolism
  • Drug Discovery*
  • Humans
  • Papillon-Lefevre Disease / genetics
  • Papillon-Lefevre Disease / pathology
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / metabolism
  • Protease Inhibitors / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / pathology
  • SARS-CoV-2 / isolation & purification
  • Serine Endopeptidases / metabolism

Substances

  • Anti-Inflammatory Agents
  • Protease Inhibitors
  • Cathepsin C
  • Serine Endopeptidases