The Future of Cysteine Cathepsins in Disease Management

Trends in Pharmacological Sciences

Volumn 38, Issue 10, 2017, Pages 873-898

  Kramer, Lovro ^a   Turk, Dušan ^a,b   Turk, Boris ^a,b,c  

^a JO EF STEFAN INSTITUTE   (Slovenia)

^b Center of Excellence CIPKEBIP   (Slovenia)

^c UNIVERSITY OF LJUBLJANA   (Slovenia)

Author keywords

[No Author keywords available]

Indexed keywords

ADCT 402; AGS 15E; AGS 67E; ARX 788; ASG 5ME; BALICATIB; BRENTUXIMAB VEDOTIN; CATHEPSIN; CATHEPSIN B; CATHEPSIN B INHIBITOR; CATHEPSIN F; CATHEPSIN H; CATHEPSIN K; CATHEPSIN K INHIBITOR; CATHEPSIN L; CATHEPSIN O; CATHEPSIN S; CATHEPSIN S INHIBITOR; CATHEPSIN V; CATHEPSIN W; CATHEPSIN X; COFETUZUMAB PELIDOTIN; CRA 028129; CT 2106; CYSTEINE CATHEPSIN; DIPEPTIDYL PEPTIDASE I; DLYE 5953A; ENFORTUMAB VEDOTIN; GLEMBATUMUMAB VEDOTIN; GSK 2793660; INDUSATUMAB VEDOTIN; LIFASTUZUMAB VEDOTIN; LY 3000328; MDX 1203; MIV 711; ODANACATIB; ONO 5334; PINATUZUMAB VEDOTIN; PK 1; PK 2; POLATUZUMAB VEDOTIN; RG 7458; RG 7625; RO 5459072; ROVALPITUZUMAB TESIRINE; RWJ 445380; SACITUZUMAB GOVITECAN; SAR 114137; SGN CD 123A; SGN CD70A; SGN LIV 1A; SGNCD 19B; TISOTUMAB VEDOTIN; TRASTUZUMAB DUOCARMAZINE; UNCLASSIFIED DRUG; UNINDEXED DRUG; VADASTUXIMAB TALIRINE; VBY 036; VBY 376; VBY 891; ANTIBODY CONJUGATE; CYSTEINE; ENZYME INHIBITOR;

AUTOIMMUNE DISEASE; CARDIOVASCULAR DISEASE; ENZYME ACTIVITY; ENZYME INDUCTION; ENZYME INHIBITION; ENZYME RELEASE; ENZYME SPECIFICITY; ENZYME STRUCTURE; HUMAN; HYDROLYSIS; IMMUNE DYSREGULATION; IMMUNE RESPONSE; IMMUNOCOMPETENT CELL; INFLAMMATION; INTRACELLULAR SIGNALING; MALIGNANT NEOPLASM; NEUROPATHIC PAIN; NONHUMAN; OSTEOLYSIS; OSTEOPOROSIS; PRIORITY JOURNAL; REVIEW; TUMOR MICROENVIRONMENT; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; DRUG DELIVERY SYSTEM; ENZYMOLOGY; METABOLISM;

ANIMALS; CATHEPSINS; CYSTEINE; DRUG DELIVERY SYSTEMS; ENZYME INHIBITORS; HUMANS; IMMUNOCONJUGATES; INFLAMMATION;

EID: 85021380787     PISSN: 01656147     EISSN: 18733735     Source Type: Journal    
DOI: 10.1016/j.tips.2017.06.003     Document Type: Review

References (201)

1. Turk, B., Targeting proteases: successes, failures and future prospects. Nat. Rev. Drug Discov. 5 (2006), 785–799.
2. Drag, M., Salvesen, G.S., Emerging principles in protease-based drug discovery. Nat. Rev. Drug Discov. 9 (2010), 690–701.
3. Turk, B., et al. Protease signalling: the cutting edge. EMBO J. 31 (2012), 1630–1643.
4. Reiser, J., et al. Specialized roles for cysteine cathepsins in health and disease. J. Clin. Invest. 120 (2010), 3421–3431.
5. Vasiljeva, O., et al. Emerging roles of cysteine cathepsins in disease and their potential as drug targets. Curr. Pharm. Des. 13 (2007), 387–403.
6. Tang, C.H., et al. Murine cathepsin F deficiency causes neuronal lipofuscinosis and late-onset neurological disease. Mol. Cell. Biol. 26 (2006), 2309–2316.
7. Smith, K.R., et al. Cathepsin F mutations cause type B Kufs disease, an adult-onset neuronal ceroid lipofuscinosis. Hum. Mol. Genet. 22 (2013), 1417–1423.
8. Stoka, V., et al. Lysosomal cathepsins and their regulation in aging and neurodegeneration. Ageing Res. Rev. 32 (2016), 22–37.
9. Fonović, M., Turk, B., Cysteine cathepsins and extracellular matrix degradation. Biochim. Biophys. Acta 1840 (2014), 2560–2570.
10. Turk, V., et al. Cysteine cathepsins: from structure, function and regulation to new frontiers. Biochim. Biophys. Acta 1824 (2012), 68–88.
11. Nakagawa, T.Y., et al. Impaired invariant chain degradation and antigen presentation and diminished collagen-induced arthritis in cathepsin S null mice. Immunity 10 (1999), 207–217.
12. Shi, G.P., et al. Cathepsin S required for normal MHC class II peptide loading and germinal center development. Immunity 10 (1999), 197–206.
13. Saftig, P., et al. Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice. Proc. Natl. Acad. Sci. U. S. A. 95 (1998), 13453–13458.
14. Bossard, M.J., et al. Proteolytic activity of human osteoclast cathepsin K expression, purification, activation, and substrate identification. J. Biol. Chem. 271 (1996), 12517–12524.
15. Olson, O.C., Joyce, J.A., Cysteine cathepsin proteases: regulators of cancer progression and therapeutic response. Nat. Rev. Cancer 15 (2015), 712–729.
16. Brömme, D., et al. Cathepsin K osteoporosis trials, pycnodysostosis and mouse deficiency models: commonalities and differences. Expert Opin. Drug Discov. 11 (2016), 457–472.
17. Qin, Y., Shi, G.P., Cysteinyl cathepsins and mast cell proteases in the pathogenesis and therapeutics of cardiovascular diseases. Pharmacol. Ther. 131 (2011), 338–350.
18. Kavčič, N., et al. Lysosomes in programmed cell death pathways: from initiators to amplifiers. Biol. Chem. 398 (2017), 289–301.
19. Sanman, L.E., Bogyo, M., Activity-based profiling of proteases. Annu. Rev. Biochem. 83 (2014), 249–273.
20. Unanue, E.R., et al. Variations in MHC class II antigen processing and presentation in health and disease. Annu. Rev. Immunol. 34 (2016), 265–297.
21. Nakagawa, T., et al. Cathepsin L: critical role in Ii degradation and CD4 T cell selection in the thymus. Science 280 (1998), 450–453.
22. Tolosa, E., et al. Cathepsin V is involved in the degradation of invariant chain in human thymus and is overexpressed in myasthenia gravis. J. Clin. Invest. 112 (2003), 517–526.
23. Stoeckle, C., et al. Cathepsin S dominates autoantigen processing in human thymic dendritic cells. J. Autoimmun. 38 (2012), 332–343.
24. Bird, P.I., et al. Endolysosomal proteases and their inhibitors in immunity. Nat. Rev. Immunol. 9 (2009), 871–882.
25. Matthews, S.P., et al. Distinct protease requirements for antigen presentation in vitro and in vivo. J. Immunol. 184 (2010), 2423–2431.
26. Garcia-Cattaneo, A., et al. Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 9053–9058.
27. Asagiri, M., et al. Cathepsin K-dependent Toll-like receptor 9 signaling revealed in experimental arthritis. Science 319 (2008), 624–627.
28. Ewald, S.E., et al. Nucleic acid recognition by Toll-like receptors is coupled to stepwise processing by cathepsins and asparagine endopeptidase. J. Exp. Med. 208 (2011), 643–651.
29. Pribis, J.P., et al. The HIV protease inhibitor saquinavir inhibits HMGB1 driven inflammation by targeting the interaction of cathepsin V with TLR4/MyD88. Mol. Med. 21 (2015), 749–757.
30. Qi, X., et al. Cathepsin B modulates lysosomal biogenesis and host defense against Francisella novicida infection. J. Exp. Med. 213 (2016), 2081–2097.
31. Sardiello, M., et al. A gene network regulating lysosomal biogenesis and function. Science 325 (2009), 473–477.
32. Deussing, J., et al. Cathepsins B and D are dispensable for major histocompatibility complex class II-mediated antigen presentation. Proc. Natl. Acad. Sci. U. S. A. 95 (1998), 4516–4521.
33. Gonzalez-Leal, I.J., et al. Cathepsin B in antigen-presenting cells controls mediators of the Th1 immune response during Leishmania major infection. PLoS Negl. Trop. Dis., 8, 2014, e3194.
34. Ha, S.D., et al. Cathepsin B is involved in the trafficking of TNF-alpha-containing vesicles to the plasma membrane in macrophages. J. Immunol. 181 (2008), 690–697.
35. Pham, C.T., Ley, T.J., Dipeptidyl peptidase I is required for the processing and activation of granzymes A and B in vivo. Proc. Natl. Acad. Sci. U. S. A. 96 (1999), 8627–8632.
36. Wolters, P.J., et al. Dipeptidyl peptidase I is essential for activation of mast cell chymases, but not tryptases, in mice. J. Biol. Chem. 276 (2001), 18551–18556.
37. Adkison, A.M., et al. Dipeptidyl peptidase I activates neutrophil-derived serine proteases and regulates the development of acute experimental arthritis. J. Clin. Invest. 109 (2002), 363–371.
38. D'Angelo, M.E., et al. Cathepsin H is an additional convertase of pro-granzyme B. J. Biol. Chem. 285 (2010), 20514–20519.
39. Sobotič, B., et al. Proteomic identification of cysteine cathepsin substrates shed from the surface of cancer cells. Mol. Cell. Proteomics 14 (2015), 2213–2228.
40. Repnik, U., et al. Cysteine cathepsins activate ELR chemokines and inactivate non-ELR chemokines. J. Biol. Chem. 290 (2015), 13800–13811.
41. Caglič, D., et al. The proinflammatory cytokines interleukin-1alpha and tumor necrosis factor alpha promote the expression and secretion of proteolytically active cathepsin S from human chondrocytes. Biol. Chem. 394 (2013), 307–316.
42. Yan, D., et al. STAT3 and STAT6 signaling pathways synergize to promote cathepsin secretion from macrophages via IRE1alpha activation. Cell Rep. 16 (2016), 2914–2927.
43. Caglič, D., et al. Glycosaminoglycans facilitate procathepsin B activation through disruption of propeptide–mature enzyme interactions. J. Biol. Chem. 282 (2007), 33076–33085.
44. Cremasco, V., et al. Protein kinase C-delta deficiency perturbs bone homeostasis by selective uncoupling of cathepsin K secretion and ruffled border formation in osteoclasts. J. Bone Miner. Res. 27 (2012), 2452–2463.
45. Garnero, P., et al. The collagenolytic activity of cathepsin K is unique among mammalian proteinases. J. Biol. Chem. 273 (1998), 32347–32352.
46. Balkan, W., et al. Identification of NFAT binding sites that mediate stimulation of cathepsin K promoter activity by RANK ligand. Gene 446 (2009), 90–98.
47. Aguda, A.H., et al. Structural basis of collagen fiber degradation by cathepsin K. Proc. Natl. Acad. Sci. U. S. A. 111 (2014), 17474–17479.
48. Brömme, D., Lecaille, F., Cathepsin K inhibitors for osteoporosis and potential off-target effects. Expert Opin. Investig. Drugs 18 (2009), 585–600.
49. Li, Z., et al. Regulation of collagenase activities of human cathepsins by glycosaminoglycans. J. Biol. Chem. 279 (2004), 5470–5479.
50. Panwar, P., et al. A novel approach to inhibit bone resorption: exosite inhibitors against cathepsin K. Br. J. Pharmacol. 173 (2016), 396–410.
51. Dejica, V.M., et al. Cleavage of type II collagen by cathepsin K in human osteoarthritic cartilage. Am. J. Pathol. 173 (2008), 161–169.
52. Duong, L.T., et al. Efficacy of a cathepsin K inhibitor in a preclinical model for prevention and treatment of breast cancer bone metastasis. Mol. Cancer Ther. 13 (2014), 2898–2909.
53. Herroon, M.K., et al. Macrophage cathepsin K promotes prostate tumor progression in bone. Oncogene 32 (2013), 1580–1593.
54. Sukhova, G.K., et al. Expression of the elastolytic cathepsins S and K in human atheroma and regulation of their production in smooth muscle cells. J. Clin. Invest. 102 (1998), 576–583.
55. Sun, J., et al. Cathepsin K deficiency reduces elastase perfusion-induced abdominal aortic aneurysms in mice. Arterioscler. Thromb. Vasc. Biol. 32 (2012), 15–23.
56. Lutgens, E., et al. Disruption of the cathepsin K gene reduces atherosclerosis progression and induces plaque fibrosis but accelerates macrophage foam cell formation. Circulation 113 (2006), 98–107.
57. Grace, P.M., et al. Pathological pain and the neuroimmune interface. Nat. Rev. Immunol. 14 (2014), 217–231.
58. Wolf, Y., et al. Microglia, seen from the CX3CR1 angle. Front. Cell. Neurosci., 7, 2013, 26.
59. Clark, A.K., et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 10655–10660.
60. Chapman, G.A., et al. Fractalkine cleavage from neuronal membranes represents an acute event in the inflammatory response to excitotoxic brain damage. J. Neurosci., 20, 2000, RC87.
61. Zhao, P., et al. Cathepsin S causes inflammatory pain via biased agonism of PAR2 and TRPV4. J. Biol. Chem. 289 (2014), 27215–27234.
62. Cattaruzza, F., et al. Cathepsin S is activated during colitis and causes visceral hyperalgesia by a PAR2-dependent mechanism in mice. Gastroenterology 141 (2011), 1864–1874.
63. Reddy, V.B., et al. Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs. Nat. Commun., 6, 2015, 7864.
64. Stellos, K., et al. Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation. Nat. Med. 22 (2016), 1140–1150.
65. Jadhav, P.K., et al. Discovery of cathepsin S inhibitor LY3000328 for the treatment of abdominal aortic aneurysm. ACS Med. Chem. Lett. 5 (2014), 1138–1142.
66. Aikawa, E., et al. Arterial and aortic valve calcification abolished by elastolytic cathepsin S deficiency in chronic renal disease. Circulation 119 (2009), 1785–1794.
67. Figueiredo, J.L., et al. Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease. Am. J. Pathol. 185 (2015), 1156–1166.
68. Clark, A.K., et al. Spinal cathepsin S and fractalkine contribute to chronic pain in the collagen-induced arthritis model. Arthritis Rheum. 64 (2012), 2038–2047.
69. Mohamed, M.M., Sloane, B.F., Cysteine cathepsins: multifunctional enzymes in cancer. Nat. Rev. Cancer 6 (2006), 764–775.
70. Pislar, A., et al. Lysosomal cysteine peptidases − molecules signaling tumor cell death and survival. Semin. Cancer Biol. 35 (2015), 168–179.
71. Sevenich, L., et al. Synergistic antitumor effects of combined cathepsin B and cathepsin Z deficiencies on breast cancer progression and metastasis in mice. Proc. Natl. Acad. Sci. U. S. A. 107 (2010), 2497–2502.
72. Gocheva, V., et al. Distinct roles for cysteine cathepsin genes in multistage tumorigenesis. Genes. Dev. 20 (2006), 543–556.
73. Akkari, L., et al. Combined deletion of cathepsin protease family members reveals compensatory mechanisms in cancer. Genes. Dev. 30 (2016), 220–232.
74. Ruffell, B., et al. Cathepsin C is a tissue-specific regulator of squamous carcinogenesis. Genes. Dev. 27 (2013), 2086–2098.
75. Dennemarker, J., et al. Deficiency for the cysteine protease cathepsin L promotes tumor progression in mouse epidermis. Oncogene 29 (2010), 1611–1621.
76. Gopinathan, A., et al. Cathepsin B promotes the progression of pancreatic ductal adenocarcinoma in mice. Gut 61 (2012), 877–884.
77. Gocheva, V., et al. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 24 (2010), 241–255.
78. Akkari, L., et al. Distinct functions of macrophage-derived and cancer cell-derived cathepsin Z combine to promote tumor malignancy via interactions with the extracellular matrix. Genes Dev. 28 (2014), 2134–2150.
79. Small, D.M., et al. Cathepsin S from both tumor and tumor-associated cells promote cancer growth and neovascularization. Int. J. Cancer 133 (2013), 2102–2112.
80. Shree, T., et al. Macrophages and cathepsin proteases blunt chemotherapeutic response in breast cancer. Genes Dev. 25 (2011), 2465–2479.
81. Vasiljeva, O., et al. Tumor cell-derived and macrophage-derived cathepsin B promotes progression and lung metastasis of mammary cancer. Cancer Res. 66 (2006), 5242–5250.
82. Lewis, C.E., et al. The multifaceted role of perivascular macrophages in tumors. Cancer Cell 30 (2016), 18–25.
83. Mohamed, M.M., et al. Interleukin-6 increases expression and secretion of cathepsin B by breast tumor-associated monocytes. Cell. Physiol. Biochem. 25 (2010), 315–324.
84. Brignull, L.M., et al. Reprogramming of lysosomal gene expression by interleukin-4 and Stat6. BMC Genomics, 14, 2013, 853.
85. Chang, S.H., et al. VEGF-A induces angiogenesis by perturbing the cathepsin-cysteine protease inhibitor balance in venules, causing basement membrane degradation and mother vessel formation. Cancer Res. 69 (2009), 4537–4544.
86. Wang, B., et al. Cathepsin S controls angiogenesis and tumor growth via matrix-derived angiogenic factors. J. Biol. Chem. 281 (2006), 6020–6029.
87. Abboud-Jarrous, G., et al. Cathepsin L. 1 is responsible for processing and activation of proheparanase through multiple cleavages of a linker segment. J. Biol. Chem. 283 (2008), 18167–18176.
88. Veillard, F., et al. Cysteine cathepsins S and L modulate anti-angiogenic activities of human endostatin. J. Biol. Chem. 286 (2011), 37158–37167.
89. Sevenich, L., et al. Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S. Nat. Cell Biol. 16 (2014), 876–888.
90. Bruchard, M., et al. Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat. Med. 19 (2013), 57–64.
91. Hornung, V., et al. Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9 (2008), 847–856.
92. Sharp, F.A., et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome. Proc. Natl. Acad. Sci. U. S. A. 106 (2009), 870–875.
93. Duewell, P., et al. NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals. Nature 464 (2010), 1357–1361.
94. Orlowski, G.M., et al. Multiple cathepsins promote pro-IL-1beta synthesis and NLRP3-mediated IL-1beta activation. J. Immunol. 195 (2015), 1685–1697.
95. Newman, Z.L., et al. CA-074Me protection against anthrax lethal toxin. Infect. Immun. 77 (2009), 4327–4336.
96. Maher, K., et al. A role for stefin B (cystatin B) in inflammation and endotoxemia. J. Biol. Chem. 289 (2014), 31736–31750.
97. Orlowski, G.M., et al. Multiple cathepsins promote inflammasome-independent, particle-induced cell death during NLRP3-dependent IL-1beta activation. J. Leukoc. Biol., 2017, 10.1189/jlb.3HI0316-152R Published online January 13, 2017.
98. Turk, V., et al. Lysosomal cysteine proteases: facts and opportunities. EMBO J. 20 (2001), 4629–4633.
99. Turk, B., et al. Lysosomal cysteine proteases: more than scavengers. Biochim. Biophys. Acta 1477 (2000), 98–111.
100. Schechter, I., Berger, A., On the size of the active site in proteases. I. Papain. Biochem. Biophys. Res. Commun. 27 (1967), 157–162.
101. Turk, D., et al. Revised definition of substrate binding sites of papain-like cysteine proteases. Biol. Chem. 379 (1998), 137–147.
102. Kirschke, H., et al. Proteinases 1: lysosomal cysteine proteinases. Protein Profile 2 (1995), 1581–1643.
103. Choe, Y., et al. Substrate profiling of cysteine proteases using a combinatorial peptide library identifies functionally unique specificities. J. Biol. Chem. 281 (2006), 12824–12832.
104. Vizovišek, M., et al. Fast profiling of protease specificity reveals similar substrate specificities for cathepsins K, L and S. Proteomics 15 (2015), 2479–2490.
105. Vidmar, R., et al. Protease cleavage site fingerprinting by label-free in-gel degradomics reveals novel pH-dependent specificity switch of legumain. EMBO J. 36 (2017), 2455–2465.
106. O'Donoghue, A.J., et al. Global identification of peptidase specificity by multiplex substrate profiling. Nat. Methods 9 (2012), 1095–1100.
107. Biniossek, M.L., et al. Proteomic identification of protease cleavage sites characterizes prime and non-prime specificity of cysteine cathepsins B, L, and S. J. Proteome Res. 10 (2011), 5363–5373.
108. Costantino, C.M., et al. Lysosomal cysteine and aspartic proteases are heterogeneously expressed and act redundantly to initiate human invariant chain degradation. J. Immunol. 180 (2008), 2876–2885.
109. Cirman, T., et al. Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. J. Biol. Chem. 279 (2004), 3578–3587.
110. Prudova, A., et al. TAILS N-terminomics and proteomics show protein degradation dominates over proteolytic processing by cathepsins in pancreatic tumors. Cell Rep. 16 (2016), 1762–1773.
111. Turk, D., Gunčar, G., Lysosomal cysteine proteases (cathepsins): promising drug targets. Acta Crystallogr. D Biol. Crystallogr. 59 (2003), 203–213.
112. Thompson, S.K., et al. Design of potent and selective human cathepsin K inhibitors that span the active site. Proc. Natl. Acad. Sci. U. S. A. 94 (1997), 14249–14254.
113. McGrath, M.E., et al. Crystal structure of human cathepsin K complexed with a potent inhibitor. Nat. Struct. Biol. 4 (1997), 105–109.
114. Lee-Dutra, A., et al. Cathepsin S inhibitors: 2004–2010. Expert Opin. Ther. Pat. 21 (2011), 311–337.
115. Deaton, D.N., Kumar, S., Cathepsin K inhibitors: their potential as anti-osteoporosis agents. Prog. Med. Chem. 42 (2004), 245–375.
116. Gauthier, J.Y., et al. The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K. Bioorg. Med. Chem. Lett. 18 (2008), 923–928.
117. Borišek, J., et al. Development of N-(functionalized benzoyl)-homocycloleucyl-glycinonitriles as potent cathepsin K inhibitors. J. Med. Chem. 58 (2015), 6928–6937.
118. Law, S., et al. Identification of mouse cathepsin K structural elements that regulate the potency of odanacatib. Biochem. J. 474 (2017), 851–864.
119. Dossetter, A.G., et al. (1R,2R)-N-(1-cyanocyclopropyl)-2-(6-methoxy-1,3,4,5-tetrahydropyrido[4,3-b]indole -2-carbonyl)cyclohexanecarboxamide (AZD4996): a potent and highly selective cathepsin K inhibitor for the treatment of osteoarthritis. J. Med. Chem. 55 (2012), 6363–6374.
120. Wiener, J.J., et al. Discovery and SAR of novel pyrazole-based thioethers as cathepsin S inhibitors. Part 2: modification of P3, P4, and P5 regions. Bioorg. Med. Chem. Lett. 20 (2010), 2375–2378.
121. Asaad, N., et al. Dipeptidyl nitrile inhibitors of cathepsin L. Bioorg. Med. Chem. Lett. 19 (2009), 4280–4283.
122. Ng, N.M., et al. Subsite cooperativity in protease specificity. Biol. Chem. 390 (2009), 401–407.
123. Desmarais, S., et al. Pharmacological inhibitors to identify roles of cathepsin K in cell-based studies: a comparison of available tools. Biol. Chem. 390 (2009), 941–948.
124. Marquis, R.W., et al. Azepanone-based inhibitors of human and rat cathepsin K. J. Med. Chem. 44 (2001), 1380–1395.
125. Stroup, G.B., et al. Potent and selective inhibition of human cathepsin K leads to inhibition of bone resorption in vivo in a nonhuman primate. J. Bone Miner. Res. 16 (2001), 1739–1746.
126. Jerome, C., et al. Balicatib, a cathepsin K inhibitor, stimulates periosteal bone formation in monkeys. Osteoporos. Int. 22 (2011), 3001–3011.
127. Falgueyret, J.P., et al. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity. J. Med. Chem. 48 (2005), 7535–7543.
128. Desmarais, S., et al. Effect of cathepsin K inhibitor basicity on in vivo off-target activities. Mol. Pharmacol. 73 (2008), 147–156.
129. Eastell, R., et al. Effect of ONO-5334 on bone mineral density and biochemical markers of bone turnover in postmenopausal osteoporosis: 2-year results from the OCEAN study. J. Bone Miner. Res. 29 (2014), 458–466.
130. Engelke, K., et al. The effect of the cathepsin K inhibitor ONO-5334 on trabecular and cortical bone in postmenopausal osteoporosis: the OCEAN study. J. Bone Miner. Res. 29 (2014), 629–638.
131. Bone, H.G., et al. Odanacatib, a cathepsin-K inhibitor for osteoporosis: a two-year study in postmenopausal women with low bone density. J. Bone Miner. Res. 25 (2010), 937–947.
132. Chapurlat, R.D., Odanacatib: a review of its potential in the management of osteoporosis in postmenopausal women. Ther. Adv. Musculoskelet. Dis. 7 (2015), 103–109.
133. Mullard, A., Merck & Co. drops osteoporosis drug odanacatib. Nat. Rev. Drug Discov., 15, 2016 669–669.
134. Feng, S., et al. Efficacy and safety of odanacatib treatment for patients with osteoporosis: a meta-analysis. J. Bone Miner. Metab. 33 (2015), 448–454.
135. Lindstrom, E., et al. Inhibition of CTX-II release by cathepsin K inhibition in vivo but not in vitro suggests that anti-resorptive therapy protects cartilage. Osteoarthritis Cartilage, 23, 2015, A310.
136. Hayami, T., et al. Inhibition of cathepsin K reduces cartilage degeneration in the anterior cruciate ligament transection rabbit and murine models of osteoarthritis. Bone 50 (2012), 1250–1259.
137. Burston, J., et al. The cathepsin K inhibitor L-006235 has analgesic and disease modifying properties in the MIA model of osteoarthritis. Osteoarthritis Cartilage, 24, 2016, S454.
138. Troeberg, L., Nagase, H., Proteases involved in cartilage matrix degradation in osteoarthritis. Biochim. Biophys. Acta 1824 (2012), 133–145.
139. Everts, V., et al. Cathepsin K deficiency in pycnodysostosis results in accumulation of non-digested phagocytosed collagen in fibroblasts. Calcif. Tissue Int. 73 (2003), 380–386.
140. Buhling, F., et al. Pivotal role of cathepsin K in lung fibrosis. Am. J. Pathol. 164 (2004), 2203–2216.
141. Friedrichs, B., et al. Thyroid functions of mouse cathepsins B, K, and L. J. Clin. Invest. 111 (2003), 1733–1745.
142. Godat, E., et al. Cathepsin K: a cysteine protease with unique kinin-degrading properties. Biochem. J. 383 (2004), 501–506.
143. Yu, N.Y., et al. Local co-delivery of rhBMP-2 and cathepsin K inhibitor L006235 in poly(d,l-lactide-co-glycolide) nanospheres. J. Biomed. Mater. Res. B Appl. Biomater. 105 (2017), 136–144.
144. Sharma, V., et al. Structural requirements for the collagenase and elastase activity of cathepsin K and its selective inhibition by an exosite inhibitor. Biochem. J. 465 (2015), 163–173.
145. Novinec, M., et al. A novel allosteric mechanism in the cysteine peptidase cathepsin K discovered by computational methods. Nat. Commun., 5, 2014, 3287.
146. Baugh, M., et al. Therapeutic dosing of an orally active, selective cathepsin S inhibitor suppresses disease in models of autoimmunity. J. Autoimmun. 36 (2011), 201–209.
147. Deschamps, K., et al. Genetic and pharmacological evaluation of cathepsin s in a mouse model of asthma. Am. J. Respir. Cell Mol. Biol. 45 (2011), 81–87.
148. Yang, H., et al. Cathepsin S is required for murine autoimmune myasthenia gravis pathogenesis. J. Immunol. 174 (2005), 1729–1737.
149. Holsinger, L.J., et al. Characterization of VBY-129, a cathepsin S inhibitor efficacious in a mouse model of psoriasis. J. Invest. Dermatol., 129, 2009.
150. Hamm-Alvarez, S.F., et al. Tear cathepsin S as a candidate biomarker for Sjogren's syndrome. Arthritis Rheumatol. 66 (2014), 1872–1881.
151. Rupanagudi, K.V., et al. Cathepsin S inhibition suppresses systemic lupus erythematosus and lupus nephritis because cathepsin S is essential for MHC class II-mediated CD4 T cell and B cell priming. Ann. Rheum. Dis. 74 (2015), 452–463.
152. Hewitt, E., et al. Selective cathepsin S inhibition with MIV-247 attenuates mechanical allodynia and enhances the antiallodynic effects of gabapentin and pregabalin in a mouse model of neuropathic pain. J. Pharmacol. Exp. Ther. 358 (2016), 387–396.
153. Irie, O., et al. Overcoming hERG issues for brain-penetrating cathepsin S inhibitors: 2-cyanopyrimidines. Part 2. Bioorg. Med. Chem. Lett. 18 (2008), 5280–5284.
154. Payne, C.D., et al. Pharmacokinetics and pharmacodynamics of the cathepsin S inhibitor, LY3000328, in healthy subjects. Br. J. Clin. Pharmacol. 78 (2014), 1334–1342.
155. Knezevic, N.N., et al. Discontinued neuropathic pain therapy between 2009-2015. Expert Opin. Investig. Drugs 24 (2015), 1631–1646.
156. Guay, D., et al. Therapeutic utility and medicinal chemistry of cathepsin C inhibitors. Curr. Top. Med. Chem. 10 (2010), 708–716.
157. Methot, N., et al. In vivo inhibition of serine protease processing requires a high fractional inhibition of cathepsin C. Mol. Pharmacol. 73 (2008), 1857–1865.
158. Schurigt, U., et al. Trial of the cysteine cathepsin inhibitor JPM-OEt on early and advanced mammary cancer stages in the MMTV-PyMT-transgenic mouse model. Biol. Chem. 389 (2008), 1067–1074.
159. Withana, N.P., et al. Cathepsin B inhibition limits bone metastasis in breast cancer. Cancer Res. 72 (2012), 1199–1209.
160. Mikhaylov, G., et al. Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment. Nat. Nanotechnol. 6 (2011), 594–602.
161. Elie, B.T., et al. Identification and preclinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model. Biochimie 92 (2010), 1618–1624.
162. Salpeter, S.J., et al. A novel cysteine cathepsin inhibitor yields macrophage cell death and mammary tumor regression. Oncogene 34 (2015), 6066–6078.
163. Mirkovic, B., et al. Nitroxoline impairs tumor progression in vitro and in vivo by regulating cathepsin B activity. Oncotarget 6 (2015), 19027–19042.
164. Wilkinson, R.D., et al. A bioavailable cathepsin S nitrile inhibitor abrogates tumor development. Mol. Cancer, 15, 2016, 29.
165. Sudhan, D.R., et al. Cathepsin L in tumor angiogenesis and its therapeutic intervention by the small molecule inhibitor KGP94. Clin. Exp. Metastasis 33 (2016), 461–473.
166. Alishekevitz, D., et al. Macrophage-induced lymphangiogenesis and metastasis following paclitaxel chemotherapy is regulated by VEGFR3. Cell Rep. 17 (2016), 1344–1356.
167. Burden, R.E., et al. Inhibition of Cathepsin S by Fsn0503 enhances the efficacy of chemotherapy in colorectal carcinomas. Biochimie 94 (2012), 487–493.
168. Gangoda, L., et al. Inhibition of cathepsin proteases attenuates migration and sensitizes aggressive N-Myc amplified human neuroblastoma cells to doxorubicin. Oncotarget 6 (2015), 11175–11190.
169. Alamir, I., et al. Beneficial effects of cathepsin inhibition to prevent chemotherapy-induced intestinal mucositis. Clin. Exp. Immunol. 162 (2010), 298–305.
170. Abd-Elrahman, I., et al. Characterizing cathepsin activity and macrophage subtypes in excised human carotid plaques. Stroke 47 (2016), 1101–1108.
171. Hu, H.Y., et al. In vivo imaging of mouse tumors by a lipidated cathepsin S substrate. Angew. Chem. Int. Ed. Engl. 53 (2014), 7669–7673.
172. Vermeij, E.A., et al. In vivo molecular imaging of cathepsin and matrix metalloproteinase activity discriminates between arthritic and osteoarthritic processes in mice. Mol. Imaging 13 (2014), 1–10.
173. Caglič, D., et al. Functional in vivo imaging of cysteine cathepsin activity in murine model of inflammation. Bioorg. Med. Chem. 19 (2011), 1055–1061.
174. Withana, N.P., et al. Non-invasive imaging of idiopathic pulmonary fibrosis using cathepsin protease probes. Sci. Rep., 6, 2016, 19755.
175. Blum, G., et al. Noninvasive optical imaging of cysteine protease activity using fluorescently quenched activity-based probes. Nat. Chem. Biol. 3 (2007), 668–677.
176. Watzke, A., et al. Selective activity-based probes for cysteine cathepsins. Angew. Chem. Int. Ed. Engl. 47 (2008), 406–409.
177. Verdoes, M., et al. Improved quenched fluorescent probe for imaging of cysteine cathepsin activity. J. Am. Chem. Soc. 135 (2013), 14726–14730.
178. Whitley, M.J., et al. A mouse–human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer. Sci. Transl. Med., 8, 2016, 320ra324.
179. Eward, W.C., et al. A novel imaging system permits real-time in vivo tumor bed assessment after resection of naturally occurring sarcomas in dogs. Clin. Orthop. Relat. Res. 471 (2013), 834–842.
180. Mito, J.K., et al. Intraoperative detection and removal of microscopic residual sarcoma using wide-field imaging. Cancer 118 (2012), 5320–5330.
181. Garland, M., et al. A bright future for precision medicine: advances in fluorescent chemical probe design and their clinical application. Cell Chem. Biol. 23 (2016), 122–136.
182. Withana, N.P., et al. Dual-modality activity-based probes as molecular imaging agents for vascular inflammation. J. Nucl. Med. 57 (2016), 1583–1590.
183. Mikhaylov, G., et al. Selective targeting of tumor and stromal cells by a nanocarrier system displaying lipidated cathepsin B inhibitor. Angew. Chem. Int. Ed. Engl. 53 (2014), 10077–10081.
184. Haris, M., et al. In vivo magnetic resonance imaging of tumor protease activity. Sci. Rep., 4, 2014, 6081.
185. Kramer, L., et al. Non-invasive in vivo imaging of tumour-associated cathepsin B by a highly selective inhibitory DARPin. Theranostics 7 (2017), 2806–2821.
186. Withana, N.P., et al. Labeling of active proteases in fresh-frozen tissues by topical application of quenched activity-based probes. Nat. Protoc. 11 (2016), 184–191.
187. Srinivasarao, M., et al. Principles in the design of ligand-targeted cancer therapeutics and imaging agents. Nat. Rev. Drug Discov. 14 (2015), 203–219.
188. Vandooren, J., et al. Proteases in cancer drug delivery. Adv. Drug Deliv. Rev. 97 (2016), 144–155.
189. de Goeij, B.E., Lambert, J.M., New developments for antibody–drug conjugate-based therapeutic approaches. Curr. Opin. Immunol. 40 (2016), 14–23.
190. Kern, J.C., et al. Novel phosphate modified cathepsin B linkers: improving aqueous solubility and enhancing payload scope of ADCs. Bioconjug. Chem. 27 (2016), 2081–2088.
191. Jain, N., et al. Current ADC linker chemistry. Pharm. Res. 32 (2015), 3526–3540.
192. Dorywalska, M., et al. Molecular basis of valine-citrulline-PABC linker instability in site-specific ADCs and its mitigation by linker design. Mol. Cancer Ther. 15 (2016), 958–970.
193. Katz, J., et al. Brentuximab vedotin (SGN-35). Clin. Cancer Res. 17 (2011), 6428–6436.
194. Gebleux, R., et al. Non-internalizing antibody-drug conjugates display potent anti-cancer activity upon proteolytic release of monomethyl auristatin E in the subendothelial extracellular matrix. Int. J. Cancer 140 (2017), 1670–1679.
195. Shaffer, S.A., et al. In vitro and in vivo metabolism of paclitaxel poliglumex: identification of metabolites and active proteases. Cancer Chemother. Pharmacol. 59 (2007), 537–548.
196. Langer, C.J., et al. Phase III trial comparing paclitaxel poliglumex (CT-2103, PPX) in combination with carboplatin versus standard paclitaxel and carboplatin in the treatment of PS 2 patients with chemotherapy-naive advanced non-small cell lung cancer. J. Thorac. Oncol. 3 (2008), 623–630.
197. Ben-Nun, Y., et al. Photodynamic quenched cathepsin activity based probes for cancer detection and macrophage targeted therapy. Theranostics 5 (2015), 847–862.
198. Shon, S.M., et al. Photodynamic therapy using a protease-mediated theranostic agent reduces cathepsin-B activity in mouse atheromata in vivo. Arterioscler. Thromb. Vasc. Biol. 33 (2013), 1360–1365.
199. Musil, D., et al. The refined 2.15 Å X-ray crystal structure of human liver cathepsin B: the structural basis for its specificity. EMBO J. 10 (1991), 2321–2330.
200. Guncar, G., et al. Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. EMBO J. 18 (1999), 793–803.
201. Turk, D., et al. Structure of human dipeptidyl peptidase I (cathepsin C): exclusion domain added to an endopeptidase framework creates the machine for activation of granular serine proteases. EMBO J. 20 (2001), 6570–6582.