Table 1.

Potential therapeutic approaches to target MPO.

Molecule	Species	Disease/Model	Key Mechanisms	Effects on Disease	References
Blocking Enzymatic Activities
4-Aminobenzoic acid hydrazide (4-ABAH)	Rabbit	Atherosclerosis	Irreversible inhibition of HOCl production	↓ Peroxidase activity	[132]
	Mice	Lung carcinoma		↓ Tumor progression	[133]
	Mice	Ischemic stroke		↑ Cell proliferation and neurogenesis	[69]
Polyamine-Conjugated Piperidine Nitroxides	Bovine	Aortic endothelial cells	↓ H2O2↓ HOCl, •NO2 scavenging	↓ Endothelial HOCl ↓ Protein nitration, ↓ NO oxidation	[134]
AZM198 (2-thioxanthin)	Mice	Obesity and hypertension	Irreversibly inhibition by covalent attachment to the heme group	↓ Body weight ↓ Fat accumulation, ↓ Inflammation ↓ Non-alcoholic steatohepatitis	[135]
	Mice	Vascular inflammation		↑eNOS/NO	[136]
	Mice	Peritonitis		↓ Tissue damage	[137]
	Guinea pig	Chronic obstructive pulmonary disease		↓ Tissue damage and remodeling	[138]
	Mice	Nephritis		↓ MPO deposition ↓ Glomerular damage	[139]
AZD3241 (Pyrrolo (3, 2-d) pyrimidin-4-one derivative)	Human	Parkinson’s disease	Selective and irreversible MPO inhibitor	↓ Neuro-inflammation	[140]
	Mice	Multiple system atrophy		↓ Microglial activation and motor impairment	[141,142]
	Mice	Colitis		↓ Weight loss ↑ Clinical score	[143]
PF-1355 (Thiouracil derivative)	Mice	Small vessel vasculitis	Irreversible MPO inhibitor	↓ HOCl ↓ Vascular edema, ↓ Neutrophil recruitment	[144]
PF-06282999 (Thiouracil derivative)	Human		Irreversible MPO inhibitor		[145]
AZD4831	Human	Heart failure with preserved ejection fraction	Selective extracellular MPO inhibitor	↓ Morbidity and mortality	[146,147]
Suppression of MPO gene expression
Atorvastatin	Human	Acute coronary syndrome	?	↓ Serum MPO	[148]
	Human	Diabetes with renal failure	?	↓ Serum MPO	[149]
All-trans retinoic acid (tretinoin)	Human	ANCA vasculitis	?	↓ Disease relapse ?	[150]
Inhibition of granule trafficking, docking and degranulation
Nexinhib 20	Mice	Endotoxemia	Selective inhibition of release of azurophilic granules	↓ Neutrophil infiltration	[151]
	Mice	Myocardial ischemia-reperfusion injury		↓ Neutrophil recruitment and exocytosis ↓ Infarct size	[152]
TAT-STX-4	Human	Neutrophils (L. monocytogenes infection)	Inhibition of degranulation	↓ Degranulation of all granule subsets	[153]
TAT-SNAP-23	Human	Neutrophils (S. aureus infection)	Inhibition of azurophilic granule release	↓ Exocytosis ↓ Respiratory burst	[154]
	Rats Mice	Acute lung injury		↓ Neutrophil recruitment ↓ Exocytosis	[155,156]
15-epi-lipoxin A4 and 17-epi-resolvin D1	Human		Activation of ALX/FPR2	↓ MPO release ↑ Phagocytosis and bacterial killing	[39]
	Mice	Acute lung injury		↑ Bacterial clearance ↑ Resolution	[39]
Targeting NETs and MPO auto-antigens
4-Aminobenzoic acid hydrazide (4-ABAH)	Human	Neutrophils		↓ NET formation	[157]
Deoxyribonuclease I (DNase I)	Human Mice	Bacterial infection	NET degradation	↓ Reactive oxygen species	[158]
N-a-benzoyl-N5-(2-chloro-1-iminoethyl)-L-ornithine am-ide (Cl-amidine)	Mice	Rheumatoid arthritis	Peptidyl arginine deiminase (1-4) inhibitor	↓ Disease severity	[159]
	Mice	Atherosclerosis		↓ Lesion area ↓ Neutrophil and macrophages recruitment	[160]
	Mice	ANCA vasculitis		↓ MPO-ANCA production	[161]
13-series resolvins (RvTs)	Human	Neutrophils		↓ MPO release ↓ NET formation ↑ NET degradation	[162]
	Mice	Bacterial infection (Skin air pouch)		↓ Neutrophil accumulation ↑ Bacterial clearance	[162]

ALX/FPR2, lipoxin A receptor/formyl peptide receptor 2; ANCA, anti-neutrophil cytoplasmic antibody; eNOS, endothelial nitric oxide synthase; NET, neutrophil extracellular traps; Nexinhib20, neutrophil granule-specific exocytosis inhibitor 20; RvTs, 13-series of resolvins. ↓ decrease; ↑ increase; ? not defined