Table 1.

Inhibitors against LMP-related cathepsins and associated diseases

LMP Cathepsins	Active Site Amino Acid	Inhibitor		Associated Diseases/References/Study Details
		Experimental Reagent	Drug Candidate
Cathepsin B	Cysteine	Ca-074 (CA-074-Me) E64d	PADK	Cancer Lung Disease, RA, OA Neurodegenerative Diseases	Appelqvist 2013, Review; Gondi 2004, mice injected via tail vein and evaluated for 72 h; Reiser 2010, Review; Sevenich 2010, knockout mice; Tummalapalli 2007, in vitro; Vasiljeva 2006, in vitro
Cathepsin C (Dipeptidyl Peptidase I)	Cysteine	Semi-carbazides Non-peptidic Cyanamides Dipeptide-derived Nitriles	Semi-carbazides Non-peptidic Cyanamides Dipeptide-derived Nitriles	Immune Disorders Lung Diseases	Laine 2010, Review; Reiser 2010, Review
Cathepsin D	Aspartic Acid	Pepstatin A Hydroxyethyl-amine isosteres	Pepstatin A derivatives Hydroxyethyl-amine isosteres	Cancer Alzheimer’s Disease	McConnell 2006, in vitro; Yan 1999, in vitro
Cathepsin H	Cysteine	Cystatins α2-macroglobulin		Cancer, Lung Diseases	Gocheva 2006, knockout mice and 2010, in vitro and in vivo; Reiser 2010, Review
Cathepsin K	Cysteine		Odanacatib MIV-711 Balicatib Relicatib ONO-5334 SAR114137	Atherosclerosis, Cancer,Metabolic Syndrome Lung Disease, RA, OA, Osteoporosis	Buhling 2004, mice and humans; Dejica 2008, humans; Duong 2016, Review; Fonovic 2014, Review; Gocheva 2006, knockout mice and 2010, in vitro and in vivo; Lutgens 2006, knockout mice; Schurigt 2008, transgenic mice; Svelander 2009, daily dose (25 mg/kg) in mice for 14 days; Yang 2008, humans
Cathepsin L	Cysteine	Z-FY-CHO PADK		Atherosclerosis Cancer Metabolic Syndrome Lung Disease Immune Disorders RA, osteoarthritis	Gocheva 2006, knockout mice and 2010 in vitro and in vivo; Honey 2002, in vitro and in vivo; Hsieh 2002, in vitro; Huang 2003, diabetic mice; Kitamoto 2007, knockout mice; Maehr 2005, diabetic mice; Nakagawa 1999, cathepsin null mice; Reiser 2010, Review
Cathepsin S	Cysteine	Cystatin C Paecilopeptin LHVS	RWJ-445380 VBY-036 VBY-891 CRA-028129 SAR114137	Atherosclerosis Cancer Metabolic Syndrome, lung disease, OA Immune Disorders Rheumatoid Arthritis Neuropathic Pain Psoriasis Abdominal Aortic Aneurism	Fonovic 2014, Review; Gocheva 2006, knockout mice and 2010, in vitro and in vivo; Hsieh 2002, in vitro; Nakagawa 1999, cathepsin null mice; Payne 2014, humans; Sukhova 2003, LDL deficient mice; Reiser 2010, Review

RA, rheumatoid arthritis; OA, osteoarthritis; LHVS morpholinurea-leucine-homophenylalanine-vinylsulfone-phenyl; PADK, Z-phe-ala-diazomethylketone