Brensoacatib regulates neutrophil activation by specifically inhibiting DPP1 enzyme, thereby reducing the release of inflammatory mediators and improving the pathological process of bronchiectasis. Its mechanism of action involves multi-level cascade reaction regulation, which will be analyzed in detail at the molecular level below.

1DPP1 enzyme inhibition mechanism

(1) Brisoprolol selectively binds to the DPP1 active site, blocking the enzyme's activation of neutrophil serine proteasome.

(2) DPP1, as a lysosomal cysteine protease, is normally responsible for cleaving the N-terminal propeptide of serine protease precursor.

(3) Drug inhibition causes neutrophil elastase, protease G, and other enzymes to remain in an inactive precursor state.

Regulation of neutrophil activity

(1) Unactivated serine proteases are unable to degrade extracellular matrix and reduce tissue destructive inflammatory responses.

(2) Reduce the release of neutrophil chemokines and inhibit the recruitment of neutrophils at the site of inflammation.

(3) By reducing the production of reactive oxygen species (ROS), the damage to the airway caused by oxidative stress can be alleviated.

3 cascade reaction blocking effect

(1) Inhibit the formation of neutrophil extracellular traps (NETs) and block the vicious cycle of chronic inflammation.

(2) Downregulate the expression of pro-inflammatory cytokines such as IL-1 β and TNF - α, and improve the local microenvironment.

(3) By regulating the protease antiprotease balance, the structural integrity of lung parenchyma is protected.

4 Pharmacodynamic characteristics

(1) The maximum inhibitory effect is achieved 6 hours after oral administration, and the effect can last for 24 hours.

(2) The activity of neutrophil elastase in bronchoalveolar lavage fluid decreased by more than 50%.

(3) Long term treatment can significantly reduce sputum neutrophil count and inflammatory marker levels.