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image of The Cathepsin Family in Disease: From Molecular Mechanisms to Therapeutic Applications

Abstract

T4he cathepsin family of proteolytic enzymes is involved in the maintenance of major physiological processes, including protein degradation, immune modulation, tissue remodeling, and apoptosis. Members of the cathepsin family include cysteine, serine, and aspartic proteases, which are implicated in diverse cellular functions. Evidence for tissue-specific expression emphasizes the specialized functions of these enzymes in many organs. However, dysregulated cathepsin activity has been implicated in a wide range of pathological conditions, including, but not limited to, cancer, cardiovascular diseases, neurodegeneration, and autoimmune disorders. There is significant therapeutic potential for intervention, whereby specific inhibitors of certain cathepsins may offer promising strategies for disease management. Despite this promise, major challenges persist in designing inhibitors that avoid off-target effects while respecting the dual physiological and pathological roles of cathepsins. Structural similarities among family members and their context-dependent functions complicate precision targeting. This review identifies the emerging strategies including structure-guided design, cathepsin-cleavable delivery systems, and real-time imaging that are reshaping therapeutic approaches toward these complex enzymes. A structured web-based literature search was conducted using PubMed, Scopus, and Google Scholar employing keywords such as “cathepsins”, “therapeutic targeting”, “proteolytic enzymes”, and “disease pathways” to inform this review. As cathepsins continue to play a key role in health and disease, much research is warranted to determine their full therapeutic potential, which would represent a foundation for treatment options for various complex diseases.

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2025-08-08
2025-10-28

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References

  1. Joyce J.A. Baruch A. Chehade K. Meyer-Morse N. Giraudo E. Tsai F.Y. Greenbaum D.C. Hager J.H. Bogyo M. Hanahan D. Cathepsin cysteine proteases are effectors of invasive growth and angiogenesis during multistage tumorigenesis. Cancer Cell 2004 5 5 443 453 10.1016/S1535‑6108(04)00111‑4 15144952
    [Google Scholar]
  2. Vidak E. Javoršek U. Vizovišek M. Turk B. Cysteine cathepsins and their extracellular roles: Shaping the microenvironment. Cells 2019 8 3 264 10.3390/cells8030264 30897858
    [Google Scholar]
  3. Liu C.L. Guo J. Zhang X. Sukhova G.K. Libby P. Shi G.P. Cysteine protease cathepsins in cardiovascular disease: From basic research to clinical trials. Nat. Rev. Cardiol. 2018 15 6 351 370 10.1038/s41569‑018‑0002‑3 29679024
    [Google Scholar]
  4. Maheshwari S. Patel B.M. Unravelling the role of cathepsins in cardiovascular diseases. Mol. Biol. Rep. 2024 51 1 579 10.1007/s11033‑024‑09518‑1 38668953
    [Google Scholar]
  5. Aghdassi A.A. Pham C. Zierke L. Mariaule V. Korkmaz B. Rhimi M. Cathepsin C role in inflammatory gastroenterological, renal, rheumatic, and pulmonary disorders. Biochimie 2024 216 175 180 10.1016/j.biochi.2023.09.018 37758158
    [Google Scholar]
  6. Wang H.L. Narisawa M. Wu P. Meng X. Cheng X.W. The many roles of cathepsins in restenosis. Heliyon 2024 10 3 24720 10.1016/j.heliyon.2024.e24720 38333869
    [Google Scholar]
  7. Yusufujiang A. Zeng S. Li H. Cathepsins and Parkinson’s disease: Insights from Mendelian randomization analyses. Front. Aging Neurosci. 2024 16 1380483 10.3389/fnagi.2024.1380483 38903897
    [Google Scholar]
  8. Olson O.C. Joyce J.A. Cysteine cathepsin proteases: Regulators of cancer progression and therapeutic response. Nat. Rev. Cancer 2015 15 12 712 729 10.1038/nrc4027 26597527
    [Google Scholar]
  9. Taleb S. Clément K. Emerging role of cathepsin S in obesity and its associated diseases. Clin. Chem. Lab. Med. 2007 45 3 328 332 10.1515/CCLM.2007.083 17378727
    [Google Scholar]
  10. Zeng R. Zhou Z. Liao W. Guo B. Genetic insights into the role of cathepsins in cardiovascular diseases: A Mendelian randomization study. ESC Heart Fail. 2024 11 5 2707 2718 10.1002/ehf2.14826 38714485
    [Google Scholar]
  11. Rudzińska M. Parodi A. Maslova V.D. Efremov Y.M. Gorokhovets N.V. Makarov V.A. Popkov V.A. Golovin A.V. Zernii E.Y. Zamyatnin A.A. Cysteine cathepsins inhibition affects their expression and human renal cancer cell phenotype. Cancers 2020 12 5 1310 10.3390/cancers12051310 32455715
    [Google Scholar]
  12. Senjor E. Kos J. Nanut M.P. Cysteine cathepsins as therapeutic targets in immune regulation and immune disorders. Biomedicines 2023 11 2 476 10.3390/biomedicines11020476 36831012
    [Google Scholar]
  13. Turk V. Turk B. Gunčar G. Turk D. Kos J. Lysosomal cathepsins: Structure, role in antigen processing and presentation, and cancer. Adv. Enzyme Regul. 2002 42 285 303 10.1016/S0065‑2571(01)00034‑6 12123721
    [Google Scholar]
  14. Li Y. Li X. Zhang P. Chen D. Tao X. Cao M. Li C. Fu Q. Genome-wide identification, evolutionary analysis, and expression patterns of cathepsin superfamily in black rockfish (Sebastes schlegelii) following Aeromonas salmonicida infection. Mar. Drugs 2022 20 8 504 10.3390/md20080504 36005507
    [Google Scholar]
  15. Brix K. Dunkhorst A. Mayer K. Jordans S. Cysteine cathepsins: Cellular roadmap to different functions. Biochimie 2008 90 2 194 207 10.1016/j.biochi.2007.07.024 17825974
    [Google Scholar]
  16. Conus S. Simon H.U. Cathepsins: Key modulators of cell death and inflammatory responses. Biochem. Pharmacol. 2008 76 11 1374 1382 10.1016/j.bcp.2008.07.041 18762176
    [Google Scholar]
  17. Guha S. Padh H. Cathepsins: Fundamental effectors of endolysosomal proteolysis. Indian J. Biochem. Biophys. 2008 45 2 75 90
    [Google Scholar]
  18. Kuester D. Lippert H. Roessner A. Krueger S. The cathepsin family and their role in colorectal cancer. Pathol. Res. Pract. 2008 204 7 491 500 10.1016/j.prp.2008.04.010 18573619
    [Google Scholar]
  19. Yadati T. Houben T. Bitorina A. Shiri-Sverdlov R. The ins and outs of cathepsins: Physiological function and role in disease management. Cells 2020 9 7 1679 10.3390/cells9071679 32668602
    [Google Scholar]
  20. Dai R. Wu Z. Chu H.Y. Lu J. Lyu A. Liu J. Zhang G. Cathepsin K. The action in and beyond bone. Front. Cell Dev. Biol. 2020 8 433 10.3389/fcell.2020.00433 32582709
    [Google Scholar]
  21. Pišlar A. Bolčina L. Kos J. New insights into the role of cysteine cathepsins in neuroinflammation. Biomolecules 2021 11 12 1796 10.3390/biom11121796 34944440
    [Google Scholar]
  22. Gonçalves R.V. Costa A.M.A. Grzeskowiak L. Oxidative stress and tissue repair: Mechanism, biomarkers, and therapeutics. Oxid. Med. Cell. Longev. 2021 2021 1 6204096 10.1155/2021/6204096 33728020
    [Google Scholar]
  23. Patel S. Homaei A. El-Seedi H.R. Akhtar N. Cathepsins: Proteases that are vital for survival but can also be fatal. Biomed. Pharmacother. 2018 105 526 532 10.1016/j.biopha.2018.05.148 29885636
    [Google Scholar]
  24. Verma S. Dixit R. Pandey K.C. Cysteine proteases: Modes of activation and future prospects as pharmacological targets. Front. Pharmacol. 2016 7 107 10.3389/fphar.2016.00107 27199750
    [Google Scholar]
  25. Ozhelvaci F. Steczkiewicz K. Identification and classification of papain-like cysteine proteinases. J. Biol. Chem. 2023 299 6 104801 10.1016/j.jbc.2023.104801 37164157
    [Google Scholar]
  26. Manchanda M. Fatima N. Chauhan S.S. Physiological and Pathological Functions of Cysteine Cathepsins. Proteases in Physiology and Pathology. Chakraborti S. Dhalla N.S. Singapore Springer Singapore 2017 217 256 10.1007/978‑981‑10‑2513‑6_11
    [Google Scholar]
  27. Drobny A. Prieto Huarcaya S. Dobert J. Kluge A. Bunk J. Schlothauer T. Zunke F. The role of lysosomal cathepsins in neurodegeneration: Mechanistic insights, diagnostic potential and therapeutic approaches. Biochim. Biophys. Acta Mol. Cell Res. 2022 1869 7 119243 10.1016/j.bbamcr.2022.119243 35217144
    [Google Scholar]
  28. Todd A.E. Orengo C.A. Thornton J.M. Evolution of protein function, from a structural perspective. Curr. Opin. Chem. Biol. 1999 3 5 548 556 10.1016/S1367‑5931(99)00007‑1 10508675
    [Google Scholar]
  29. Sun M. Chen M. Liu Y. Fukuoka M. Zhou K. Li G. Dawood F. Gramolini A. Liu P.P. Cathepsin-L contributes to cardiac repair and remodelling post-infarction. Cardiovasc. Res. 2011 89 2 374 383 10.1093/cvr/cvq328 21147810
    [Google Scholar]
  30. Klaus V. Schmies F. Reeps C. Trenner M. Geisbüsch S. Lohoefer F. Eckstein H.H. Pelisek J. Cathepsin S is associated with degradation of collagen I in abdominal aortic aneurysm. Vasa 2018 47 4 285 293 10.1024/0301‑1526/a000701 29624112
    [Google Scholar]
  31. Xie Z. Zhao M. Yan C. Kong W. Lan F. Narengaowa Zhao S. Yang Q. Bai Z. Qing H. Ni J. Cathepsin B in programmed cell death machinery: Mechanisms of execution and regulatory pathways. Cell Death Dis. 2023 14 4 255 10.1038/s41419‑023‑05786‑0 37031185
    [Google Scholar]
  32. Kroemer G. Jäättelä M. Lysosomes and autophagy in cell death control. Nat. Rev. Cancer 2005 5 11 886 897 10.1038/nrc1738 16239905
    [Google Scholar]
  33. Nagakannan P. Islam M.I. Conrad M. Eftekharpour E. Cathepsin B is an executioner of ferroptosis. Biochim. Biophys. Acta Mol. Cell Res. 2021 1868 3 118928 10.1016/j.bbamcr.2020.118928 33340545
    [Google Scholar]
  34. Silver J. Tran A.P. Cathepsins in neuronal plasticity. Neural Regen. Res. 2021 16 1 26 35 10.4103/1673‑5374.286948 32788444
    [Google Scholar]
  35. Zhao P. Sun T. Lyu C. Liang K. Du Y. Cell mediated ECM-degradation as an emerging tool for anti-fibrotic strategy. Cell Regen. 2023 12 1 29 10.1186/s13619‑023‑00172‑9 37653282
    [Google Scholar]
  36. Therrien C. Lachance P. Sulea T. Purisima E.O. Qi H. Ziomek E. Alvarez-Hernandez A. Roush W.R. Ménard R. Cathepsins X and B can be differentiated through their respective mono- and dipeptidyl carboxypeptidase activities. Biochemistry 2001 40 9 2702 2711 10.1021/bi002460a 11258881
    [Google Scholar]
  37. Reiser J. Adair B. Reinheckel T. Specialized roles for cysteine cathepsins in health and disease. J. Clin. Invest. 2010 120 10 3421 3431 10.1172/JCI42918 20921628
    [Google Scholar]
  38. Gul I. Abbas M.N. Kausar S. Luo J. Gao X. Mu Y. Fan W. Cui H. Insight into crustacean cathepsins: Structure-evolutionary relationships and functional roles in physiological processes. Fish Shellfish Immunol. 2023 139 108852 10.1016/j.fsi.2023.108852 37295735
    [Google Scholar]
  39. Benton M.L. Abraham A. LaBella A.L. Abbot P. Rokas A. Capra J.A. The influence of evolutionary history on human health and disease. Nat. Rev. Genet. 2021 22 5 269 283 10.1038/s41576‑020‑00305‑9 33408383
    [Google Scholar]
  40. Borensztejn K. Tyrna P. Gaweł A.M. Dziuba I. Wojcik C. Bialy L.P. Mlynarczuk-Bialy I. Classification of cell-in-cell structures: Different phenomena with similar appearance. Cells 2021 10 10 2569 10.3390/cells10102569 34685548
    [Google Scholar]
  41. Pečar Fonović U. Kos J. Mitrović A. Compensational role between cathepsins. Biochimie 2024 226 62 76 10.1016/j.biochi.2024.04.010 38663456
    [Google Scholar]
  42. Ni J. Lan F. Xu Y. Nakanishi H. Li X. Extralysosomal cathepsin B in central nervous system: Mechanisms and therapeutic implications. Brain Pathol. 2022 32 5 13071 10.1111/bpa.13071 35411983
    [Google Scholar]
  43. Vizovišek M. Fonović M. Turk B. Cysteine cathepsins in extracellular matrix remodeling: Extracellular matrix degradation and beyond. Matrix Biol. 2019 75-76 141 159 10.1016/j.matbio.2018.01.024 29409929
    [Google Scholar]
  44. Keerthi N. Farhana A. Das D. Banerjee A. Pathak S. Role of proteolytic enzymes. Handbook of Proteases in Cancer: Cellular and Molecular Aspects. Cham Springer 2021 10.1007/978‑3‑030‑57334‑4_5
    [Google Scholar]
  45. Angadi P.V. Cathepsins as diagnostic and prognostic markers in oral cancer. Pathophysiological Aspects of Proteases in Cancer. Amsterdam, Netherlands Elsevier 2025 239 252 10.1016/B978‑0‑443‑30098‑1.00015‑X
    [Google Scholar]
  46. Chaturvedi S. Mishra A.K. Chaudhary V. Singh V.P. Singh K. Emerging proteases for molecular imaging and therapy in cancer. Handbook of Proteases in Cancer. Boca Raton, Florida CRC Press 2024 337 360
    [Google Scholar]
  47. Wang H. Jiang H. Cheng X.W. Cathepsin S are involved in human carotid atherosclerotic disease progression, mainly by mediating phagosomes: Bioinformatics and in vivo and vitro experiments. PeerJ 2022 10 12846 10.7717/peerj.12846 35186462
    [Google Scholar]
  48. Pan L. Li Y. Jia L. Qin Y. Qi G. Cheng J. Qi Y. Li H. Du J. Cathepsin S deficiency results in abnormal accumulation of autophagosomes in macrophages and enhances Ang II-induced cardiac inflammation. PLoS One 2012 7 4 35315 10.1371/journal.pone.0035315 22558139
    [Google Scholar]
  49. Padmini R. Lavanya M. Cathepsins, chemoresistance, and cancer. Pathophysiological Aspects of Proteases in Cancer. Amsterdam, Netherlands Elsevier 2025 363 384 10.1016/B978‑0‑443‑30098‑1.00022‑7
    [Google Scholar]
  50. Stoka V. Vasiljeva O. Nakanishi H. Turk V. The role of cysteine protease cathepsins B, H, C, and X/Z in neurodegenerative diseases and cancer. Int. J. Mol. Sci. 2023 24 21 15613 10.3390/ijms242115613 37958596
    [Google Scholar]
  51. Liu X.H. Liu X.T. Wu Y. Li S.A. Ren K.D. Cheng M. Huang B. Yang Y. Liu P.P. Broadening Horizons: Exploring the cathepsin family as therapeutic targets for Alzheimer’s disease. Aging Dis. 2024 16 0 10.14336/AD.2024.0456 39122455
    [Google Scholar]
  52. Shen X.B. Chen X. Zhang Z.Y. Wu F.F. Liu X.H. Cathepsin C inhibitors as anti-inflammatory drug discovery: Challenges and opportunities. Eur. J. Med. Chem. 2021 225 113818 10.1016/j.ejmech.2021.113818 34492551
    [Google Scholar]
  53. Korkmaz B. Lamort A.S. Domain R. Beauvillain C. Gieldon A. Yildirim A.Ö. Stathopoulos G.T. Rhimi M. Jenne D.E. Kettritz R. Cathepsin C inhibition as a potential treatment strategy in cancer. Biochem. Pharmacol. 2021 194 114803 10.1016/j.bcp.2021.114803 34678221
    [Google Scholar]
  54. Abideen S.A. Khan M. Al-Harbi A.I. Ahmad S. Pharmacological inhibition of cathepsin C (CatC) as a potential approach for cancer therapeutics. J. Biomol. Struct. Dyn. 2023 41 18 8682 8689 10.1080/07391102.2022.2135603 36264138
    [Google Scholar]
  55. Jadhav P.K. Schiffler M.A. Gavardinas K. Kim E.J. Matthews D.P. Staszak M.A. Coffey D.S. Shaw B.W. Cassidy K.C. Brier R.A. Zhang Y. Christie R.M. Matter W.F. Qing K. Durbin J.D. Wang Y. Deng G.G. Discovery of cathepsin S inhibitor LY3000328 for the treatment of abdominal aortic aneurysm. ACS Med. Chem. Lett. 2014 5 10 1138 1142 10.1021/ml500283g 25313327
    [Google Scholar]
  56. Ajani T.A. Magwebu Z.E. Chauke C.G. Obikeze K. Advances in cathepsin S inhibition: Challenges and breakthroughs in drug development. Pathophysiology 2024 31 3 471 487 10.3390/pathophysiology31030035 39311309
    [Google Scholar]
  57. Rot A.E. Hrovatin M. Bokalj B. Lavrih E. Turk B. Cysteine cathepsins: From diagnosis to targeted therapy of cancer. Biochimie 2024 226 10 28 10.1016/j.biochi.2024.09.001 39245316
    [Google Scholar]
  58. Kirschke H. Wiederanders B. Brömme D. Rinne A. Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. Biochem. J. 1989 264 2 467 473 10.1042/bj2640467 2690828
    [Google Scholar]
  59. Chitsamankhun C. Siritongtaworn N. Fournier B.P.J. Sriwattanapong K. Theerapanon T. Samaranayake L. Porntaveetus T. Cathepsin C in health and disease: From structural insights to therapeutic prospects. J. Transl. Med. 2024 22 1 777 10.1186/s12967‑024‑05589‑7 39164687
    [Google Scholar]
  60. Drake M.T. Clarke B.L. Oursler M.J. Khosla S. Cathepsin K inhibitors for osteoporosis: Biology, potential clinical utility, and lessons learned. Endocr. Rev. 2017 38 4 325 350 10.1210/er.2015‑1114 28651365
    [Google Scholar]
  61. Cai Z. Xu S. Liu C. Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies. J. Cell. Mol. Med. 2024 28 17 70064 10.1111/jcmm.70064 39248527
    [Google Scholar]
  62. Li Q. Zhou Z. Xu T. Gao X. Lou Y. Chen Z. Zhang M. Fang Q. Tan J. Huang J. Relationship between cathepsins and cardiovascular diseases: A Mendelian randomized study. Front. Pharmacol. 2024 15 1370350 10.3389/fphar.2024.1370350 39027333
    [Google Scholar]
  63. Sena B.F. Figueiredo J.L. Aikawa E. Cathepsin S. Cathepsin S as an inhibitor of cardiovascular inflammation and calcification in chronic kidney disease. Front. Cardiovasc. Med. 2018 4 88 10.3389/fcvm.2017.00088 29379789
    [Google Scholar]
  64. Figueiredo J.L. Aikawa M. Zheng C. Aaron J. Lax L. Libby P. de Lima Filho J.L. Gruener S. Fingerle J. Haap W. Hartmann G. Aikawa E. Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease. Am. J. Pathol. 2015 185 4 1156 1166 10.1016/j.ajpath.2014.11.026 25680278
    [Google Scholar]
  65. Platt M.O. Shockey W.A. Endothelial cells and cathepsins: Biochemical and biomechanical regulation. Biochimie 2016 122 314 323 10.1016/j.biochi.2015.10.010 26458976
    [Google Scholar]
  66. Douglas S.A. Lamothe S.E. Singleton T.S. Averett R.D. Platt M.O. Human cathepsins K, L, and S: Related proteases, but unique fibrinolytic activity. Biochim. Biophys. Acta, Gen. Subj. 2018 1862 9 1925 1932 10.1016/j.bbagen.2018.06.015 29944896
    [Google Scholar]
  67. Cheng X.W. Shi G.P. Kuzuya M. Sasaki T. Okumura K. Murohara T. Role for cysteine protease cathepsins in heart disease: Focus on biology and mechanisms with clinical implication. Circulation 2012 125 12 1551 1562 10.1161/CIRCULATIONAHA.111.066712 22451605
    [Google Scholar]
  68. Bian B. Mongrain S. Cagnol S. Langlois M.J. Boulanger J. Bernatchez G. Carrier J.C. Boudreau F. Rivard N. Cathepsin B promotes colorectal tumorigenesis, cell invasion, and metastasis. Mol. Carcinog. 2016 55 5 671 687 10.1002/mc.22312 25808857
    [Google Scholar]
  69. Gocheva V. Wang H.W. Gadea B.B. Shree T. Hunter K.E. Garfall A.L. Berman T. Joyce J.A. IL-4 induces cathepsin protease activity in tumor-associated macrophages to promote cancer growth and invasion. Genes Dev. 2010 24 3 241 255 10.1101/gad.1874010 20080943
    [Google Scholar]
  70. McDowell S.H. Gallaher S.A. Burden R.E. Scott C.J. Leading the invasion: The role of Cathepsin S in the tumour microenvironment. Biochim. Biophys. Acta Mol. Cell Res. 2020 1867 10 118781 10.1016/j.bbamcr.2020.118781 32544418
    [Google Scholar]
  71. Yadav S. Vashisth C. Chaudhri V. Singh K. Raghav N. Pundeer R. Development of potential cathepsin B inhibitors: Synthesis of new bithiazole derivatives, in vitro studies supported with theoretical docking studies. Int. J. Biol. Macromol. 2024 281 Pt 2 136290 10.1016/j.ijbiomac.2024.136290 39383913
    [Google Scholar]
  72. Aggarwal N. Sloane B.F. Cathepsin B: Multiple roles in cancer. Proteomics Clin. Appl. 2014 8 5-6 427 437 10.1002/prca.201300105 24677670
    [Google Scholar]
  73. Chalmers J.D. Burgel P.R. Daley C.L. De Soyza A. Haworth C.S. Mauger D. Mange K. Teper A. Fernandez C. Conroy D. Metersky M. Brensocatib in non-cystic fibrosis bronchiectasis: ASPEN protocol and baseline characteristics. ERJ Open Res. 2024 10 4 00151 02024 10.1183/23120541.00151‑2024 39040578
    [Google Scholar]
  74. Kreideweiss S. Schänzle G. Schnapp G. Vintonyak V. Grundl M.A. BI 1291583: A novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis. Inflamm. Res. 2023 72 8 1709 1717 10.1007/s00011‑023‑01774‑4 37542002
    [Google Scholar]
  75. Cipolla D. Zhang J. Korkmaz B. Chalmers J.D. Basso J. Lasala D. Fernandez C. Teper A. Mange K.C. Perkins W.R. Sullivan E.J. Dipeptidyl peptidase-1 inhibition with brensocatib reduces the activity of all major neutrophil serine proteases in patients with bronchiectasis: Results from the WILLOW trial. Respir. Res. 2023 24 1 133 10.1186/s12931‑023‑02444‑z 37198686
    [Google Scholar]
  76. Rupanagudi K.V. Kulkarni O.P. Lichtnekert J. Darisipudi M.N. Mulay S.R. Schott B. Gruner S. Haap W. Hartmann G. Anders H.J. 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. 2015 74 2 452 463 10.1136/annrheumdis‑2013‑203717 24300027
    [Google Scholar]
  77. Lee J. Jang S. Choi M. Kang M. Lim S.G. Kim S.I.Y. Jang S. Ko J. Kim E. Yi J. Choo Y. Kim M.O. Ryoo Z.Y. Overexpression of cathepsin S exacerbates lupus pathogenesis through upregulation TLR7 and IFN-α in transgenic mice. Sci. Rep. 2021 11 1 16348 10.1038/s41598‑021‑94855‑5 34381063
    [Google Scholar]
  78. Wilson S.R. Peters C. Saftig P. Brömme D. Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption. J. Biol. Chem. 2009 284 4 2584 2592 10.1074/jbc.M805280200 19028686
    [Google Scholar]
  79. Statham L.A. Aspray T.J. Odanacatib: The best osteoporosis treatment we never had? Lancet Diabetes Endocrinol. 2019 7 12 888 889 10.1016/S2213‑8587(19)30348‑1 31676223
    [Google Scholar]
  80. Anderson M.S. Gendrano I.N. Liu C. Jeffers S. Mahon C. Mehta A. Mostoller K. Zajic S. Morris D. Lee J. Stoch S.A. Odanacatib, a selective cathepsin K inhibitor, demonstrates comparable pharmacodynamics and pharmacokinetics in older men and postmenopausal women. J. Clin. Endocrinol. Metab. 2014 99 2 552 560 10.1210/jc.2013‑1688 24276460
    [Google Scholar]
  81. Lewiecki E.M. Odanacatib, a cathepsin K inhibitor for the treatment of osteoporosis and other skeletal disorders associated with excessive bone remodeling. IDrugs 2009 12 12 799 809 19943223
    [Google Scholar]
  82. Scarcella M. d’Angelo D. Ciampa M. Tafuri S. Avallone L. Pavone L.M. De Pasquale V. The key role of lysosomal protease cathepsins in viral infections. Int. J. Mol. Sci. 2022 23 16 9089 10.3390/ijms23169089 36012353
    [Google Scholar]
  83. Yoo Y. Choi E. Kim Y. Cha Y. Um E. Kim Y. Kim Y. Lee Y.S. Therapeutic potential of targeting cathepsin S in pulmonary fibrosis. Biomed. Pharmacother. 2022 145 112245 10.1016/j.biopha.2021.112245 34772578
    [Google Scholar]
  84. Zhang Y. Xu Q. Gao Z. Zhang H. Xie X. Li M. High-throughput screening for optimizing adoptive T cell therapies. Exp. Hematol. Oncol. 2024 13 1 113 10.1186/s40164‑024‑00580‑w 39538305
    [Google Scholar]
  85. Petushkova A.I. Savvateeva L.V. Zamyatnin A.A. Structure determinants defining the specificity of papain-like cysteine proteases. Comput. Struct. Biotechnol. J. 2022 20 6552 6569 10.1016/j.csbj.2022.11.040 36467578
    [Google Scholar]
  86. Lecaille F. Kaleta J. Brömme D. Human and parasitic papain-like cysteine proteases: Their role in physiology and pathology and recent developments in inhibitor design. Chem. Rev. 2002 102 12 4459 4488 10.1021/cr0101656 12475197
    [Google Scholar]
  87. Gupta S. Singh R.K. Dastidar S. Ray A. Cysteine cathepsin S as an immunomodulatory target: Present and future trends. Expert Opin. Ther. Targets 2008 12 3 291 299 10.1517/14728222.12.3.291 18269339
    [Google Scholar]
  88. Fujishima A. Imai Y. Nomura T. Fujisawa Y. Yamamoto Y. Sugawara T. The crystal structure of human cathepsin L complexed with E‐64. FEBS Lett. 1997 407 1 47 50 10.1016/S0014‑5793(97)00216‑0 9141479
    [Google Scholar]
  89. Gunčar G. Klemenčič I. Turk B. Turk V. Karaoglanovic-Carmona A. Juliano L. Turk D. Crystal structure of cathepsin X: A flip–flop of the ring of His23 allows carboxy-monopeptidase and carboxy-dipeptidase activity of the protease. Structure 2000 8 3 305 313 10.1016/S0969‑2126(00)00108‑8 10745011
    [Google Scholar]
  90. Burster T. Macmillan H. Hou T. Boehm B.O. Mellins E.D. Cathepsin G: Roles in antigen presentation and beyond. Mol. Immunol. 2010 47 4 658 665 10.1016/j.molimm.2009.10.003 19910052
    [Google Scholar]
  91. Korkmaz B. Horwitz M.S. Jenne D.E. Gauthier F. Neutrophil elastase, proteinase 3, and cathepsin G as therapeutic targets in human diseases. Pharmacol. Rev. 2010 62 4 726 759 10.1124/pr.110.002733 21079042
    [Google Scholar]
  92. Zamolodchikova T.S. Tolpygo S.M. Svirshchevskaya E.V. Cathepsin g not only inflammation: The immune protease can regulate normal physiological processes. Front. Immunol. 2020 11 411 10.3389/fimmu.2020.00411 32194574
    [Google Scholar]
  93. Zdravkova K. Mijanovic O. Brankovic A. Ilicheva P.M. Jakovleva A. Karanovic J. Pualic M. Pualic D. Rubel A.A. Savvateeva L.V. Parodi A. Zamyatnin A.A. Unveiling the roles of cysteine proteinases f and w: From structure to pathological implications and therapeutic targets. Cells 2024 13 11 917 10.3390/cells13110917 38891048
    [Google Scholar]
  94. Saftig P. Hunziker E. Everts V. Jones S. Boyde A. Wehmeyer O. Suter A. von Figura K. Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice. Adv. Exp. Med. Biol. 2002 477 293 303 10.1007/0‑306‑46826‑3_32 10849757
    [Google Scholar]
  95. Ma Y. Shang J. Liu L. Li M. Xu X. Cao H. Xu L. Sun W. Song G. Zhang X.B. Rational design of a double-locked photoacoustic probe for precise in vivo imaging of cathepsin B in atherosclerotic plaques. J. Am. Chem. Soc. 2023 145 32 17881 17891 10.1021/jacs.3c04981 37531186
    [Google Scholar]
  96. Wang Y. Zhao J. Gu Y. Wang H. Jiang M. Zhao S. Qing H. Ni J. Cathepsin H. Molecular characteristics and clues to function and mechanism. Biochem. Pharmacol. 2023 212 115585 10.1016/j.bcp.2023.115585 37148981
    [Google Scholar]
  97. Zhang X. Luo Y. Hao H. Krahn J.M. Su G. Dutcher R. Xu Y. Liu J. Pedersen L.C. Xu D. Heparan sulfate selectively inhibits the collagenase activity of cathepsin K. Matrix Biol. 2024 129 15 28 10.1016/j.matbio.2024.03.005 38548090
    [Google Scholar]
  98. Chenchar A. Cathepsin K Inhibition for Accelerating Diabetic Wound. Healing. Laramie, Wyoming University of Wyoming 2023
    [Google Scholar]
  99. Lecaille F. Brömme D. Lalmanach G. Biochemical properties and regulation of cathepsin K activity. Biochimie 2008 90 2 208 226 10.1016/j.biochi.2007.08.011 17935853
    [Google Scholar]
  100. Im E. Kazlauskas A. The role of cathepsins in ocular physiology and pathology. Exp. Eye Res. 2007 84 3 383 388 10.1016/j.exer.2006.05.017 16893541
    [Google Scholar]
  101. Cooper J. Aspartic proteinases in disease: A structural perspective. Curr. Drug Targets 2002 3 2 155 173 10.2174/1389450024605382 11958298
    [Google Scholar]
  102. Azeem M.N.A. Yassin N.Y.S. Ahmed N.A. Ahmed O.M. Role of cysteine proteases and matrix metalloproteases in apoptosis and necrosis in cancer. Handbook of Proteases in Cancer. Boca Raton, Florida CRC Press 2025 355 367
    [Google Scholar]
  103. Barchielli G. Capperucci A. Tanini D. Therapeutic cysteine protease inhibitors: A patent review (2018-present). Expert Opin. Ther. Pat. 2024 34 1-2 17 49 10.1080/13543776.2024.2327299 38445468
    [Google Scholar]
  104. Wu Y. Mumford P. Noy S. Cleverley K. Mrzyglod A. Luo D. van Dalen F. Verdoes M. Fisher E.M.C. Wiseman F.K. Cathepsin B abundance, activity and microglial localisation in Alzheimer’s disease-Down syndrome and early onset Alzheimer’s disease; the role of elevated cystatin B. Acta Neuropathol. Commun. 2023 11 1 132 10.1186/s40478‑023‑01632‑8 37580797
    [Google Scholar]
  105. Naba A. Mechanisms of assembly and remodelling of the extracellular matrix. Nat. Rev. Mol. Cell Biol. 2024 25 11 865 885 10.1038/s41580‑024‑00767‑3 39223427
    [Google Scholar]
  106. Thomas J.T. Joseph B. Waltimo T. Matrix Metalloproteinases (MMPs). Advances in Gingival Diseases and Conditions IntechOpen 2022 10.5772/intechopen.114353
    [Google Scholar]
  107. Dana D. Pathak S.K. A review of small molecule inhibitors and functional probes of human cathepsin L. Molecules 2020 25 3 698 10.3390/molecules25030698 32041276
    [Google Scholar]
  108. Stoka V. Turk V. Turk B. Lysosomal cathepsins and their regulation in aging and neurodegeneration. Ageing Res. Rev. 2016 32 22 37 10.1016/j.arr.2016.04.010 27125852
    [Google Scholar]
  109. Sato A. Shimotsuma A. Miyoshi T. Takahashi Y. Funayama N. Ogino Y. Hiramoto A. Wataya Y. Kim H.S. Extracellular leakage protein patterns in two types of cancer cell death: Necrosis and apoptosis. ACS Omega 2023 8 28 25059 25065 10.1021/acsomega.3c01691 37483236
    [Google Scholar]
  110. Sommese R.F. Ritt M. Swanson C.J. Sivaramakrishnan S. The role of regulatory domains in maintaining autoinhibition in the multidomain kinase PKCα. J. Biol. Chem. 2017 292 7 2873 2880 10.1074/jbc.M116.768457 28049730
    [Google Scholar]
  111. Turk V. Stoka V. Vasiljeva O. Renko M. Sun T. Turk B. Turk D. Cysteine cathepsins: From structure, function and regulation to new frontiers. Biochim. Biophys. Acta. Proteins Proteomics 2012 1824 1 68 88 10.1016/j.bbapap.2011.10.002 22024571
    [Google Scholar]
  112. Khan A.R. James M.N.G. Molecular mechanisms for the conversion of zymogens to active proteolytic enzymes. Protein Sci. 1998 7 4 815 836 10.1002/pro.5560070401 9568890
    [Google Scholar]
  113. Lalmanach G. Saidi A. Bigot P. Chazeirat T. Lecaille F. Wartenberg M. Regulation of the proteolytic activity of cysteine cathepsins by oxidants. Int. J. Mol. Sci. 2020 21 6 1944 10.3390/ijms21061944 32178437
    [Google Scholar]
  114. Voronina M.V. Frolova A.S. Kolesova E.P. Kuldyushev N.A. Parodi A. Zamyatnin A.A. The intricate balance between life and death: Ros, cathepsins, and their interplay in cell death and autophagy. Int. J. Mol. Sci. 2024 25 7 4087 10.3390/ijms25074087 38612897
    [Google Scholar]
  115. Mijanović O. Branković A. Panin A.N. Savchuk S. Timashev P. Ulasov I. Lesniak M.S. Cathepsin B. A sellsword of cancer progression. Cancer Lett. 2019 449 207 214 10.1016/j.canlet.2019.02.035 30796968
    [Google Scholar]
  116. Yoon M.C. Phan V. Podvin S. Mosier C. O’Donoghue A.J. Hook V. Distinct cleavage properties of cathepsin B compared to cysteine cathepsins enable the design and validation of a specific substrate for cathepsin B over a broad pH range. Biochemistry 2023 62 15 2289 2300 10.1021/acs.biochem.3c00139 37459182
    [Google Scholar]
  117. Rückrich T. Brandenburg J. Cansier A. Müller M. Stevanović S. Schilling K. Wiederanders B. Beck A. Melms A. Reich M. Driessen C. Kalbacher H. Specificity of human cathepsin S determined by processing of peptide substrates and MHC class II-associated invariant chain. Biol. Chem. 2006 387 10/11 1503 1511 10.1515/BC.2006.188 17081125
    [Google Scholar]
  118. Benes P. Vetvicka V. Fusek M. Cathepsin D. Many functions of one aspartic protease. Crit. Rev. Oncol. Hematol. 2008 68 1 12 28 10.1016/j.critrevonc.2008.02.008 18396408
    [Google Scholar]
  119. Pei X.D. Fan H.L. Jiao D.Q. Li F. He Y.N. Wu Q.L. Liu X.L. Wang C.H. Rational engineering S1′ substrate binding pocket to enhance substrate specificity and catalytic activity of thermal-stable keratinase for efficient keratin degradation. Int. J. Biol. Macromol. 2024 263 Pt 1 130688 10.1016/j.ijbiomac.2024.130688 38458294
    [Google Scholar]
  120. Selvaraj C. Rudhra O. Alothaim A.S. Alkhanani M. Singh S.K. Chapter Three - Structure and chemistry of enzymatic active sites that play a role in the switch and conformation mechanism. Advances in Protein Chemistry and Structural Biology. Donev R. United States Academic Press 2022 59 83
    [Google Scholar]
  121. Lecaille F. Chowdhury S. Purisima E. Brömme D. Lalmanach G. The S2 subsites of cathepsins K and L and their contribution to collagen degradation. Protein Sci. 2007 16 4 662 670 10.1110/ps.062666607 17384231
    [Google Scholar]
  122. Kasperkiewicz P. Poreba M. Groborz K. Drag M. Emerging challenges in the design of selective substrates, inhibitors and activity‐based probes for indistinguishable proteases. FEBS J. 2017 284 10 1518 1539 10.1111/febs.14001 28052575
    [Google Scholar]
  123. Johnson D.S. Weerapana E. Cravatt B.F. Strategies for discovering and derisking covalent, irreversible enzyme inhibitors. Future Med. Chem. 2010 2 6 949 964 10.4155/fmc.10.21 20640225
    [Google Scholar]
  124. Uitdehaag J.C.M. Verkaar F. Alwan H. de Man J. Buijsman R.C. Zaman G.J.R. A guide to picking the most selective kinase inhibitor tool compounds for pharmacological validation of drug targets. Br. J. Pharmacol. 2012 166 3 858 876 10.1111/j.1476‑5381.2012.01859.x 22250956
    [Google Scholar]
  125. Wilkinson R.D.A. Williams R. Scott C.J. Burden R.E. Cathepsin S: Therapeutic, diagnostic, and prognostic potential. Biol. Chem. 2015 396 8 867 882 10.1515/hsz‑2015‑0114
    [Google Scholar]
  126. Pišlar A. Jewett A. Kos J. Cysteine cathepsins: Their biological and molecular significance in cancer stem cells. Semin. Cancer Biol. 2018 53 168 177 10.1016/j.semcancer.2018.07.010 30063965
    [Google Scholar]
  127. Niemeyer C. Matosin N. Kaul D. Philipsen A. Gassen N.C. The role of cathepsins in memory functions and the pathophysiology of psychiatric disorders. Front. Psychiatry 2020 11 718 10.3389/fpsyt.2020.00718 32793006
    [Google Scholar]
  128. Hang H.C. Loureiro J. Spooner E. van der Velden A.W.M. Kim Y.M. Pollington A.M. Maehr R. Starnbach M.N. Ploegh H.L. Mechanism-based probe for the analysis of cathepsin cysteine proteases in living cells. ACS Chem. Biol. 2006 1 11 713 723 10.1021/cb600431a 17184136
    [Google Scholar]
  129. Montague-Cardoso K. Malcangio M. Cathepsin S as a potential therapeutic target for chronic pain. Med. Drug Discov. 2020 7 100047 10.1016/j.medidd.2020.100047 32904424
    [Google Scholar]
  130. Zhou Y. Tao L. Qiu J. Xu J. Yang X. Zhang Y. Tian X. Guan X. Cen X. Zhao Y. Tumor biomarkers for diagnosis, prognosis and targeted therapy. Signal Transduct. Target. Ther. 2024 9 1 132 10.1038/s41392‑024‑01823‑2 38763973
    [Google Scholar]
  131. Park S.H. Lee J.H. Yang S.B. Lee D.N. Kang T.B. Park J. Development of a peptide-based nano-sized cathepsin b inhibitor for anticancer therapy. Pharmaceutics 2023 15 4 1131 10.3390/pharmaceutics15041131 37111617
    [Google Scholar]
  132. Mihăilă R.G. Monoclonal antibodies, bispecific antibodies and antibody-drug conjugates in oncohematology. Recent Patents Anticancer Drug Discov. 2020 15 4 272 292 10.2174/1574892815666200925120717 32981510
    [Google Scholar]
  133. Clark A.K. Yip P.K. Grist J. Gentry C. Staniland A.A. Marchand F. Dehvari M. Wotherspoon G. Winter J. Ullah J. Bevan S. Malcangio M. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc. Natl. Acad. Sci. USA 2007 104 25 10655 10660 10.1073/pnas.0610811104 17551020
    [Google Scholar]
  134. Elie B.T. Gocheva V. Shree T. Dalrymple S.A. Holsinger L.J. Joyce J.A. Identification and pre-clinical testing of a reversible cathepsin protease inhibitor reveals anti-tumor efficacy in a pancreatic cancer model. Biochimie 2010 92 11 1618 1624 10.1016/j.biochi.2010.04.023 20447439
    [Google Scholar]
  135. Hua Y. Dai X. Xu Y. Xing G. Liu H. Lu T. Chen Y. Zhang Y. Drug repositioning: Progress and challenges in drug discovery for various diseases. Eur. J. Med. Chem. 2022 234 114239 10.1016/j.ejmech.2022.114239 35290843
    [Google Scholar]
  136. Mcgrath M.E. Palmer J.T. Brömme D. Somoza J.R. Crystal structure of human cathepsin S. Protein Sci. 1998 7 6 1294 1302 10.1002/pro.5560070604 9655332
    [Google Scholar]
  137. Satam H. Joshi K. Mangrolia U. Waghoo S. Zaidi G. Rawool S. Thakare R.P. Banday S. Mishra A.K. Das G. Malonia S.K. Next-generation sequencing technology: Current trends and advancements. Biology 2023 12 7 997 10.3390/biology12070997 37508427
    [Google Scholar]
  138. Thacharodi A. Singh P. Meenatchi R. Tawfeeq Ahmed Z.H. Kumar R.R.S. v N. Kavish S. Maqbool M. Hassan S. Revolutionizing healthcare and medicine: The impact of modern technologies for a healthier future A comprehensive review. Health. Care Science 2024 3 5 329 349 10.1002/hcs2.115 39479277
    [Google Scholar]
  139. Schade M. Merla B. Lesch B. Wagener M. Timmermanns S. Pletinckx K. Hertrampf T. Highly selective sub-nanomolar cathepsin s inhibitors by merging fragment binders with nitrile inhibitors. J. Med. Chem. 2020 63 20 11801 11808 10.1021/acs.jmedchem.0c00949 32880457
    [Google Scholar]
  140. Fuchs N. Meta M. Schuppan D. Nuhn L. Schirmeister T. Novel opportunities for cathepsin S inhibitors in cancer immunotherapy by nanocarrier-mediated delivery. Cells 2020 9 9 2021 2021 10.3390/cells9092021 32887380
    [Google Scholar]
  141. Lemke C. Benýšek J. Brajtenbach D. Breuer C. Jílková A. Horn M. Buša M. Ulrychová L. Illies A. Kubatzky K.F. Bartz U. Mareš M. Gütschow M. An activity-based probe for cathepsin k imaging with excellent potency and selectivity. J. Med. Chem. 2021 64 18 13793 13806 10.1021/acs.jmedchem.1c01178 34473502
    [Google Scholar]
  142. Liu D. Wang Y. Li X. Li M. Wu Q. Song Y. Zhu Z. Yang C. Integrated microfluidic devices for in vitro diagnostics at point of care. Aggregate 2022 3 5 184 10.1002/agt2.184
    [Google Scholar]
  143. Li Y. Mei T. Han S. Han T. Sun Y. Zhang H. An F. Cathepsin B-responsive nanodrug delivery systems for precise diagnosis and targeted therapy of malignant tumors. Chin. Chem. Lett. 2020 31 12 3027 3040 10.1016/j.cclet.2020.05.027
    [Google Scholar]
  144. Caculitan N.G. dela Cruz Chuh J. Ma Y. Zhang D. Kozak K.R. Liu Y. Pillow T.H. Sadowsky J. Cheung T.K. Phung Q. Haley B. Lee B.C. Akita R.W. Sliwkowski M.X. Polson A.G. Cathepsin B is dispensable for cellular processing of cathepsin B-cleavable antibody-drug conjugates. Cancer Res. 2017 77 24 7027 7037 10.1158/0008‑5472.CAN‑17‑2391 29046337
    [Google Scholar]
  145. Lankelma J.M. Voorend D.M. Barwari T. Koetsveld J. Van der Spek A.H. De Porto A.P.N.A. Van Rooijen G. Van Noorden C.J.F. Cathepsin L, target in cancer treatment? Life Sci. 2010 86 7-8 225 233 10.1016/j.lfs.2009.11.016 19958782
    [Google Scholar]
  146. Kramer L. Turk D. Turk B. The future of cysteine cathepsins in disease management. Trends Pharmacol. Sci. 2017 38 10 873 898 10.1016/j.tips.2017.06.003 28668224
    [Google Scholar]
  147. Kos J. Mitrović A. Mirković B. The current stage of cathepsin B inhibitors as potential anticancer agents. Future Med. Chem. 2014 6 11 1355 1371 10.4155/fmc.14.73 25163003
    [Google Scholar]
  148. Palermo C. Joyce J.A. Cysteine cathepsin proteases as pharmacological targets in cancer. Trends Pharmacol. Sci. 2008 29 1 22 28 10.1016/j.tips.2007.10.011 18037508
    [Google Scholar]
  149. Zamyatnin A.A. Gregory L.C. Townsend P.A. Soond S.M. Beyond basic research: The contribution of cathepsin B to cancer development, diagnosis and therapy. Expert Opin. Ther. Targets 2022 26 11 963 977 10.1080/14728222.2022.2161888 36562407
    [Google Scholar]
  150. Porta E.O.J. Steel P.G. Activity-based protein profiling: A graphical review. Curr. Res. Pharm. Drug Disc 2023 5 100164 10.1016/j.crphar.2023.100164 37692766
    [Google Scholar]
  151. Zhao S. Jiang M. Qing H. Ni J. Cathepsins and SARS‐CoV‐2 infection: From pathogenic factors to potential therapeutic targets. Br. J. Pharmacol. 2023 180 19 2455 2481 10.1111/bph.16187 37403614
    [Google Scholar]
  152. Zhao M.M. Yang W.L. Yang F.Y. Zhang L. Huang W.J. Hou W. Fan C.F. Jin R.H. Feng Y.M. Wang Y.C. Yang J.K. Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development. Signal Transduct. Target. Ther. 2021 6 1 134 10.1038/s41392‑021‑00558‑8 33774649
    [Google Scholar]
  153. Brown R. Nath S. Lora A. Samaha G. Elgamal Z. Kaiser R. Taggart C. Weldon S. Geraghty P. Cathepsin S: Investigating an old player in lung disease pathogenesis, comorbidities, and potential therapeutics. Respir. Res. 2020 21 1 111 10.1186/s12931‑020‑01381‑5 32398133
    [Google Scholar]
  154. Patra J.K. Das G. Fraceto L.F. Campos E.V.R. Rodriguez-Torres M.P. Acosta-Torres L.S. Diaz-Torres L.A. Grillo R. Swamy M.K. Sharma S. Habtemariam S. Shin H.S. Nano based drug delivery systems: Recent developments and future prospects. J. Nanobiotechnology 2018 16 1 71 10.1186/s12951‑018‑0392‑8 30231877
    [Google Scholar]
  155. Alqurashi H. Ortega Asencio I. Lambert D.W. The emerging potential of extracellular vesicles in cell-free tissue engineering and regenerative medicine. Tissue Eng. Part B Rev. 2021 27 5 530 538 10.1089/ten.teb.2020.0222 33126845
    [Google Scholar]
  156. Beck M. Covino R. Hänelt I. Müller-McNicoll M. Understanding the cell: Future views of structural biology. Cell 2024 187 3 545 562 10.1016/j.cell.2023.12.017 38306981
    [Google Scholar]
  157. Crucitti D. Pérez Míguez C. Díaz Arias J.Á. Fernandez Prada D.B. Mosquera Orgueira A. De novo drug design through artificial intelligence: An introduction. Front Hematol. 2024 3 10.3389/frhem.2024.1305741
    [Google Scholar]
  158. Kar K. Design of enzyme inhibitors in drug discovery. Comput. Meth Rat Drug Design 2025 311 325 10.1002/9781394249190.ch14
    [Google Scholar]
  159. Li J. Wang Q. Xia G. Adilijiang N. Li Y. Hou Z. Fan Z. Li J. Recent advances in targeted drug delivery strategy for enhancing oncotherapy. Pharmaceutics 2023 15 9 2233 10.3390/pharmaceutics15092233 37765202
    [Google Scholar]
  160. Mall J. Naseem N. Haider M.F. Rahman M.A. Khan S. Siddiqui S.N. Nanostructured lipid carriers as a drug delivery system: A comprehensive review with therapeutic applications. Intell. Pharm. 2024 3 10.1016/j.ipha.2024.09.005
    [Google Scholar]
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The Cathepsin Family in Disease: From Molecular Mechanisms to Therapeutic Applications
Bentham Science Publishers ; https://doi.org/10.2174/011570159X382799250721072924
/content/journals/cn/10.2174/011570159X382799250721072924
/content/journals/cn/10.2174/011570159X382799250721072924
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  • Article Type:     Review Article
Keywords: Cathepsins ; drug development ; pathological conditions ; proteolytic enzymes ; molecular mechanisms ; therapeutic targeting

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