Table 4.

Mode of action and therapeutic application of exogenous/synthetic NSPs inhibitors.

Inhibitor	Origin	Action	Therapeutic use	References
ONO-5046 (Sivelestat)	exogenous/synthetic	- inhibition of released and membrane bound elastase	AATD, COPD, ARSD; CKD	18, 82
ONO-6818 (Freselestat)	exogenous/synthetic	- inhibition of released and membrane bound elastase	ALI, SIRS	18, 98
AZD9668 (Alvestat)	exogenous/synthetic	- reversible inhibitor with high selectivity and target specificity	ALI, lung emphysema, COPD	18
BAY- 678	exogenous/synthetic	- reversible inhibitor with high selectivity and target specificity	ALI, lung emphysema	18
BAY-85-8501	exogenous/synthetic	- improvement in potency and inhibitory capacity for NE	anti-inflammatory in pulmonary diseases	76
4-oxo-β-lactams	exogenous/synthetic	- selective irreversivel NE inhibitor	COPD	85
MK0339	exogenous/synthetic	- cell survival enhancer - stimulator of formation of mature neutrophils	ELANE‐associated neutropenia	87
Cinnoline derivatives	exogenous/synthetic	- reversible competitive inhibitors of NE	anti-inflammatory	88
Camostat mesilate	exogenous/synthetic	- anti-oxidant	chronic pancreatitis , renoprotection in patients with salt-sensitive hypertension, slows the progression of CRF, improvement of CKD progression	92, 130, 131
SB- 656933	exogenous/synthetic	- prevention of neutrophil infiltration	CF	99
		- modulation of airway inflammation
MK-7123	exogenous/synthetic	- antagonist of the cytokine receptor CXCR2	COPD	100
Azithromycin	exogenous/synthetic	- inhibition of CXCL8 levels and bacterial load	COPD	101
Roflumistat	exogenous/synthetic	- inhibition of the AcPG pathway	COPD	102

AATD: alpha1-antitrypsin deficiency; AcPGP: acetylated proline-glycine-proline; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; CF: Cystic fibrosis; COPD: chronic obstructive pulmonary disease; CRF: chronic renal failure; CXCL8: chemokine ligand 8: CXCR2: chemokine receptor type2; NE: neutrophil elastase; SIRS systemic inflammatory response syndrome.