DPP-1 inhibitors / Cathepsin C inhibitors

see also:

• bronchiectasis

• dipeptidyl peptidase-1 (DPP-1) inhibitors (aka Cathepsin C inhibitors) are the first disease-specific therapy shown to be effective in non-cystic fibrosis bronchiectasis
• DPP-1 plays a crucial role in activating various granular serine proteases including cathepsin G (CatG), neutrophil elastase (NE) and proteinase 3 (PR3)

• suppression of activity of neutrophil serine proteases (NSPs) by preventing them from being activated during neutrophil maturation in the bone marrow.
• NSPs exert multiple directly damaging effects and contribute to ongoing dysregulated airway inflammation
• high airway levels of NSPs are linked to bronchiectasis disease severity
• brensocatib treatment in COVID-19 altered multiple neutrophil proteins including profound effects on Azu-1, identifying this as a key DPP-1 target and potentially highly sensitive biomarker of treatment efficacy¹⁾

• gastrointestinal disorders
• infections

• brensocatib (Brinsupri)
  • an oral small-molecule inhibitor of dipeptidyl peptidase 1 (DPP1) — approved for Rx of non-cystic fibrosis bronchiectasis by FDA in 2025 but not yet approved in Australia as of Jan 2026
  • did not improve clinical status at day 29 in patients hospitalised with COVID-19, in fact, these patients were clinically worse²⁾