Visceral hypersensitivity in inflammatory bowel diseases and irritable bowel syndrome: The role of proteases

Table 1 Serine protease inhibitors (mammalian): examples of clinical applications in different organ systems

Category	Indication	Serine protease inhibitor (target)	Status	Ref.
Cardiovascular	ACS	Bivalirudin (thrombin)	Approved	[73]
	AF	Rivaroxaban (factor Xa)	Approved	[74]
		Edoxaban (factor Xa)	Approved	[75]
	VTE	Dabigatran (thrombin)	Approved	[76]
Dermatology	Herpes zoster	Argatroban (thrombin)	Clinical - phase II	[77]
	Oral leukoplakia	BBIC (broad specificity)	Clinical - phase II	[78]
Hematology	Heparin-induced thrombocytopenia	Argatroban (thrombin)	Approved	[79]
		Fondaparinux (factor Xa)	Approved
Oncology	Pancreatic cancer: CTx	Upamostat (uPA)	Clinical - phase II	[80]
		Nafamostat mesilate (broad specificity)	Clinical - phase II	[81]
	Lung cancer: RTx	Ulinastatin (broad specificity)	Clinical - phase unknown	[82]
	Colorectal cancer: CTx	Talabostat (fibroblast activating protein)	Clinical - phase II	[83]
	Esophageal cancer: Sx	Ulinastatin (broad specificity)	Clinical - phase unknown	[84]
Pneumology	Asthma	APC 366 (mast cell tryptase)	Clinical - phase II	[85]
	α1 antitrypsin deficiency	α1 antitrypsin (broad specificity)	Approved	[86]
	Cystic fibrosis	α1 antitrypsin (broad specificity)	Clinical - phase II	[87]
Endocrinology	Diabetes	Gliptins (DPP-IV)1	Approved	[88]
Surgery	NA	Aprotinin (broad specificity)	Approved	[89]
		Gabexate mesilate (broad specificity)	Clinical - phase III	[90]
		Nafamostat mesilate (broad specificity)	Clinical - phase IV	[91]
		Sivelestat (neutrophil elastase)	Clinical - phase unknown	[92]

¹DPP-IV is a non-classical serine protease belonging to family S9: prolyl oligopeptidase (novel class). Literature search in Pubmed (last updated Sept 19 2016) with MeSH terms serine protease inhibitor - dpp-4 inhibitor - clinical trials - English - human. ACS: Acute coronary syndrome; A: Atrial fibrillation; BBIC: Bowman Birk inhibitor concentrate; BHR: Bronchial hyperresponsiveness; cf.: Compared to; CTx,: Chemotherapy; DPP-IV: Dipeptidylpeptidase IV; EAR: Early asthmatic response; GP: Glycoprotein IIb/IIIa inhibitor; ICH: Intracranial hemorrhage; LAR: Late asthmatic response; PA: Protease activity; PI: Protease inhibitor; POC: Postoperative complications; RTx: Radiotherapy; SIRS: Systemic inflammatory respiratory syndrome; Sx: Surgery; uPA: Urokinase plasminogen activator; VTE: Venous thromboembolism.