Skip to main content
SpringerLink
Log in

Clinical Potential of Matrix Metalloprotease Inhibitors

  • Section 1: Matrix Metalloprotease Inhibitor
  • Leading Article
  • Published:
Drugs in R & D Aims and scope Submit manuscript

Abstract

The mature extracellular matrix (ECM) is a heterogenous substance produced by a variety of cells, mostly of mesothelial origin. The ECM serves as a tissue skeleton, a medium of communication between cells and as a barrier between the cells and the vascular system. The matrix is continuously remodelled in the living tissues. A variety of proteases, including matrix metalloproteases (MMPs), contribute to matrix destruction. These proteases are neutralised by naturally occurring inhibitors such as α2-macroglobulin or tissue inhibitors of metalloproteases (TIMPs). Proteases and their inhibitors are often produced by the same cells, thus matrix remodelling is localised and strictly controlled.

The MMPs are zinc-endopeptidases functioning at a neutral pH and requiring ionised calcium for activity. The extracellular matrix is an essential part of every organ and tissue type. MMPs are the key components of the system that dynamically controls the structure and function of the ECM. MMPs have been implicated in corneal disease, periodontal disease, dermatological disorders, atherosclerosis, bone and joint disorders, fibrotic disease, vascular abnormalities, malignancy and many other pathological processes.

Several synthetic inhibitors of MMPs have been developed and many of them are currently in clinical trials. Compounds discussed in this article include batimastat, marimastat, BAY12-9566, AG-3340, OPB-3206, KBR-7785, KBR-8301, CDP-845 (CT-1746), metastat and AE-941 (Neovastat®).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Dvorak HF, Brown LF, Detmar M, et al. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability and angiogenesis. Am J Pathol 1995; 146: 1029–39

    PubMed  CAS  Google Scholar 

  2. Wojtowicz-Praga SM, Dickson RB, Hawkins MJ. Matrix metalloproteinase inhibitors. Invest New Drugs 1997; 15: 61–75

    Article  PubMed  CAS  Google Scholar 

  3. Fridman R, Toth M, Pena D, et al. Activation of progelatinase B (MMP-9) by gelatinase A (MMP-2). Cancer Res 1995; 55: 2548–55

    PubMed  CAS  Google Scholar 

  4. Nawrocki B, Polette M, Marchand V, et al. Membrane-type matrix metalloproteinase-1 expression at the site of human placentation. Placenta 1996; 17 (8): 565–72

    Article  PubMed  CAS  Google Scholar 

  5. Bischof P, Martelli M, Campana A, et al. Importance of matrix metalloproteinases in human trophoblast invasion. Early Pregnancy 1995; 1 (4): 263–9

    PubMed  CAS  Google Scholar 

  6. Vettraino IM, Roby J, Tolley T, et al. Collagenase-I, stromelysin-I, and matrilysin are expressed within the placenta during multiple stages of human pregnancy. Placenta 1996; 17 (8): 557–63

    Article  PubMed  CAS  Google Scholar 

  7. Huppertz B, Kertschanska S, Demir AY, et al. Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta. Cell Tissue Res 1997; 291 (1): 133–48

    Article  Google Scholar 

  8. Stahle-Backdahl M, Sandstedt B, Bruce K, et al. Collagenase-3 (MMP-13) is expressed during human fetal ossification and re-expressed in postnatal bone remodeling and in rheumatoid arthritis. Lab Invest 1997; 76 (5): 717–28

    PubMed  CAS  Google Scholar 

  9. Kinoh H, Sato H, Tsunezuka Y, et al. MT-MMP, the cell surface activator of proMMP-2 (pro-gelatinase A), is expressed with its substrate in mouse tissue during embryogenesis. J Cell Sci 1996; 109 (Pt 5): 953–9

    PubMed  CAS  Google Scholar 

  10. Edwards JC, Wilkinson LS, Soothill P, et al. Matrix metalloproteinases in the formation of human synovial joint cavities. J Anat 1996; 188 (Pt 2): 355–60

    PubMed  CAS  Google Scholar 

  11. Heikinheimo K, Salo T. Expression of basement membrane type IV collagen and type IV collagenases (MMP-2 and MMP-9) in human fetal teeth. J Dent Res 1995; 74 (5): 1226–34

    Article  PubMed  CAS  Google Scholar 

  12. Infeld MD. Cell-matrix interactions in gland development in the lung. Exp Lung Res 1997; 23 (2): 161–9

    Article  PubMed  CAS  Google Scholar 

  13. Sutherland RS, Baskin LS, Elfman F, et al. The role of type IV collagenases in rat bladder development and obstruction. Pediatr Res 1997; 41 (3): 430–4

    Article  PubMed  CAS  Google Scholar 

  14. Terada T, Okada Y, Nakanuma Y. Expression of matrix proteinases during human intrahepatic bile duct development: a possible role in biliary cell migration. Am J Pathol 1995; 147 (5): 1207–13

    PubMed  CAS  Google Scholar 

  15. Vadillo-Ortega F, Gonzalez-Avila G, Furth EE, et al. 92-kd type IV collagenase (matrix metalloproteinase-9) activity in human amniochorion increases with labor. Am J Pathol 1995; 146 (1): 148–56

    PubMed  CAS  Google Scholar 

  16. Folkman J, Klagsburn M. Angiogenic factors. Science 1987; 235: 442–7

    Article  PubMed  CAS  Google Scholar 

  17. Kolben M, Lopens A, Blaser J, et al. Proteases and their inhibitors are indicative in gestational disease. Eur J Obstet Gynecol Reprod Biol 1996; 68 (1–2): 59–65

    Article  Google Scholar 

  18. Maj JG, Kankofer M. Activity of 72-kDa and 92-kDa matrix metalloproteinases in placental tissues of cows with and without retained fetal membranes. Placenta 1997; 18 (8): 683–7

    Article  PubMed  CAS  Google Scholar 

  19. Koolwijk P, Miltenburg AM, van Erck MG, et al. Activated gelatinase-B (MMP-9) and urokinase-type plasminogen activator in synovial fluids of patients with arthritis: correlation with clinical and experimental variables of inflammation. J Rheumatol 1995; 22: 385–93

    PubMed  CAS  Google Scholar 

  20. Okada Y, Naka K, Kawamura K, et al. Localization of matrix metalloproteinase 9 (92-kilodalton gelatinase/type IV collagenase = gelatinase B) in osteoclasts: implications for bone resorption. Lab Invest 1995; 72: 311–22

    PubMed  CAS  Google Scholar 

  21. Yoshihara Y, Obata K, Fujimoto N, et al. Increased levels of stromelysin-1 and tissue inhibitor of metalloproteinases-1 in sera from patients with rheumatoid arthritis. Arthritis Rheum 1995; 38: 969–75

    Article  PubMed  CAS  Google Scholar 

  22. Manicourt DH, Fujimoto N, Obata K, et al. Serum levels of collagenase, stromelysin-1, and TIMP-1. Age- and sex-related differences in normal subjects and relationship to the extent of joint involvement and serum levels of antigenic keratan sulfate in patients with osteoarthritis. Arthritis Rheum 1994; 37: 1774–83

    Article  PubMed  CAS  Google Scholar 

  23. Greenwald RA. Treatment of destructive arthritic disorders with MMP inhibitors. Potential role of tetracyclines. Ann N Y Acad Sci 1994; 732: 181–98

    Article  PubMed  CAS  Google Scholar 

  24. Wojtowicz-Praga SM, Torri J, Johnson M, et al. Phase I trial of Marimastat (BB-2516), a novel matrix metalloproteinase inhibitor administered orally to patients with advanced lung cancer. J Clin Oncol 1998; 16 (6): 2150–6

    PubMed  CAS  Google Scholar 

  25. Sepper R, Konttinen YT, Ding Y, et al. Human neutrophil collagenase (MMP-8), identified in bronchiectasis BAL fluid, correlates with severity of disease. Chest 1995; 107: 1641–7

    Article  PubMed  CAS  Google Scholar 

  26. Shapiro SD. Elastolytic metalloproteinases produced by human mononuclear phagocytes: potential roles in destructive lung disease. Am J Respir Crit Care Med 1994; 150: 160–4

    Google Scholar 

  27. Bailey CJ, Hembry RM, Alexander A, et al. Distribution of the matrix metalloproteinases stromelysin, gelatinases A and B, and collagenase in Crohn’s disease and normal intestine. J Clin Pathol 1994; 47: 113–6

    Article  PubMed  CAS  Google Scholar 

  28. Takahara T, Furui K, Funaki J, et al. Increased expression of matrix metalloproteinase-II in experimental liver fibrosis in rats. Hepatology 1995; 21: 787–95

    Article  PubMed  CAS  Google Scholar 

  29. Milani S, Herbst H, Schuppan D, et al. Differential expression of matrix metalloproteinase-1 and -2 genes in normal and fibrotic human liver. Am J Pathol 1994; 144: 528–37

    PubMed  CAS  Google Scholar 

  30. Peters CA, Freeman MR, Fernandez CA, et al. Dysregulated proteolytic balance as the basis of excess extracellular matrix in fibrotic disease. Am J Physiol 1997 Jun; 272 (6 Pt 2): R1960–5

    PubMed  CAS  Google Scholar 

  31. Newman KM, Malon AM, Shin RD, et al. Matrix metalloproteinases in abdominal aortic aneurysm: characterization, purification, and their possible sources. Connect Tissue Res 1994; 30: 265–76

    Article  PubMed  CAS  Google Scholar 

  32. Irizarry E, Newman KM, Gandhi RH, et al. Demonstration of interstitial collagenase in abdominal aortic aneurysm disease. J Surg Res 1993; 54: 571–4

    Article  PubMed  CAS  Google Scholar 

  33. Wysocki AB, Staiano-Coico L, Grinnell F. Wound fluid from chronic leg ulcers contains elevated levels of metalloproteinases MMP-2 and MMP-9. J Invest Dermatol 1993; 101: 64–8

    Article  PubMed  CAS  Google Scholar 

  34. Liotta LA, Steeg PS, Stetler-Stevenson WG. Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 1991; 64: 327–36

    Article  PubMed  CAS  Google Scholar 

  35. Tryggvason K, Hoyhtya M, Pyke C. Type IV collagenases in invasive tumors. Breast Cancer Res Treat 1993; 24: 209–18

    Article  PubMed  CAS  Google Scholar 

  36. Ray JM, Stetler-Stevenson WG. Gelatinase A activity directly modulates melanoma cell adhesion and spreading. EMBO J 1995; 14: 908–17

    PubMed  CAS  Google Scholar 

  37. Zucker S, Lysik RM, Zarrabi MH, et al. Mr 92,000 Type IV collagenase is increased in plasma of patients with colon and breast cancer. Cancer Res 1993; 53: 140–6

    PubMed  CAS  Google Scholar 

  38. Brown PD, Bloxidge RE, Stuart NSA, et al. Association between expression of activated 72-kilodalton gelatinase and tumor spread in non-small cell lung carcinoma. J Natl Cancer Inst 1993; 85: 574–8

    Article  PubMed  CAS  Google Scholar 

  39. Levy TD, Cioce V, Sobel ME, et al. Increased expression of the Mr 72,000 type IV collagenase in human colonic adenocarcinoma. Cancer Res 1991; 51: 439–44

    PubMed  CAS  Google Scholar 

  40. Weidner N, Semple JP, Welch WR, et al. Tumor angiogenesis and metastasis: correlation in invasive breast carcinoma. N Engl J Med 1990; 324: 1–8

    Article  Google Scholar 

  41. Denekamp J, Hobson B. Endothelial-cell proliferation in experimental tumors. Br J Cancer 1982; 46: 711–20

    Article  PubMed  CAS  Google Scholar 

  42. Fisher C, Gilbertson-Beadling S, Powers EA, et al. Interstitial collagenase is required for angiogenesis in vitro. Dev Biol 1994; 162: 499–510

    Article  PubMed  CAS  Google Scholar 

  43. Barrett AJ, Starkey PM. The interaction of α2-macroglobulin with proteinases. Biochem J 1973; 133: 703–13

    Google Scholar 

  44. Sottrup JL, Birkedal HH. Human fibroblast collagenase-α-macroglobulin interactions: localization of cleavage sites in the bait regions of five mammalian α-macroglobulins. J Biol Chem 1989; 264: 393–401

    Google Scholar 

  45. Clark SD, Kobayashi DK, Welgus HG. Regulation of the expression of tissue inhibitor of metalloproteinases and collagenase by retinoids and glucocorticoids in human fibroblasts. J Clin Invest 1987; 80: 1280–8

    Article  PubMed  CAS  Google Scholar 

  46. Takemura M, Azuma C, Kimura T, et al. Type-IV collagenase and tissue inhibitor of metalloproteinase in ovarian cancer tissues. Int J Gynaecol Obstet 1994; 46: 303–9

    Article  PubMed  CAS  Google Scholar 

  47. Alvarez OA, Carmichael DF, DeClerck YA. Inhibition of collagenolytic activity and metastasis of tumor cells by a recombinant human tissue inhibitor of metalloproteinases. J Natl Cancer Inst 1990; 82: 589–95

    Article  PubMed  CAS  Google Scholar 

  48. Yoneda T, Sasaki A, Dunstan C, et al. Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2. J Clin Invest 1997; 99 (10): 2509–17

    Article  PubMed  CAS  Google Scholar 

  49. Apte SS, Hayashi K, Seldin MF, et al. Gene encoding a novel murine tissue inhibitor of metalloproteinases (TIMP), TIMP-3, is expressed in developing mouse epithelia, cartilage, and muscle, and is located on mouse chromosome 10. Dev Dyn 1994; 200: 177–97

    Article  PubMed  CAS  Google Scholar 

  50. Wang M, Liu YE, Greene J, et al. Inhibition of tumor growth and metastasis of human breast cancer cells transfected with tissue inhibitor of metalloproteinase 4. Oncogene 1997; 14 (23): 2767–74

    Article  PubMed  CAS  Google Scholar 

  51. Burns F, Stack MS, Gray MS, et al. Inhibition of purified collagenase from alkaline-burned rabbit corneas. Invest Ophtalmol Vis Sci 1989; 30: 1569–75

    CAS  Google Scholar 

  52. Karakiulakis G, Missirlis E, Maragoudakis ME. Basement membrane collagen-degrading activity from a malignant tumor is inhibited by anthracycline antibiotics. Biochim Biophys Acta 1990; 1035: 218–22

    Article  PubMed  CAS  Google Scholar 

  53. Izquierdo-Martin M, Stein RL. Mechanistic studies on the inhibition of stromelysin by a peptide phosphonamidate. Bioorg Med Chem 1993; 1: 19–26

    Article  PubMed  CAS  Google Scholar 

  54. Brown FK, Brown PJ, Bickett DM, et al. Matrix metalloproteinase inhibitors containing a (carboxyalkyl) amino zinc ligand: modification of the P1 and P2’ residues. J Med Chem 1994; 37: 674–88

    Google Scholar 

  55. Davies B, Brown PD, East N, et al. A synthetic matrix metalloproteinase inhibitor decreases tumor burden and prolongs survival of mice bearing human ovarian carcinoma xenografts. Cancer Res 1993; 53: 2087–91

    PubMed  CAS  Google Scholar 

  56. Low JA, Johnson MD, Bone EA, et al. The metalloproteinase inhibitor Batimastat (BB-94) retards human breast cancer solid tumor growth but not ascites formation in nude mice. Clin Cancer Res 1996; 2: 1207–14

    PubMed  CAS  Google Scholar 

  57. Wang X, Fu X, Brown PD, et al. Matrix metalloproteinase inhibitor BB-94 (Batimastat) inhibits human colon tumor growth and spread in a patient-like orthotopic model in nude mice. Cancer Res 1994; 54: 4726–8

    PubMed  CAS  Google Scholar 

  58. Chirivi RGS, Garofalo A, Crimmin MJ, et al. Inhibition of the metastatic spread and growth of B16-BL6 murine melanoma by a synthetic matrix metalloproteinase inhibitor. Int J Cancer 1994; 58: 460–4

    Article  PubMed  CAS  Google Scholar 

  59. Taraboletti G, Garofalo A, Belotti D, et al. Inhibition of angiogenesis and murine hemangioma growth by Batimastat, a synthetic inhibitor of matrix metalloproteinases. J Natl Cancer Inst 1995; 87: 293–8

    Article  PubMed  CAS  Google Scholar 

  60. Wojtowicz-Praga S, Low J, Dickson R, et al. Phase I study of Batimastat (BB-94), a novel matrix metalloproteinase inhibitor in patients with advanced cancer. Invest New Drugs 1996; 14: 193–202

    Article  PubMed  CAS  Google Scholar 

  61. Parsons SL, Watson SA, Steele RJ. Phase I/II trial of batimastat, a matrix metalloproteinase inhibitor, in patients with malignant ascites. Eur J Surg Oncol 1997; 23 (6): 526–31

    Article  PubMed  CAS  Google Scholar 

  62. Drummond AH, Beckett P, Bone EA, et al. BB-2516: an orally bioavailable matrix metalloproteinase inhibitor with efficacy in animal cancer models. 86th Annual Meeting of the American Association of Cancer Research; 1995 Mar 18–22; Toronto. Philadelphia: American Association of Cancer Research, 1995: 100

    Google Scholar 

  63. Boasberg P, Harbaugh B, Roth B, et al. Marimastat, a novel matrix metalloproteinase inhibitor in patients with hormone refractory prostate cancer. 32nd Annual Meeting of the American Society of Clinical Oncology; 1996 May 18–21; Philadelphia. Chicago: American Society of Clinical Oncology, 1996: 258

    Google Scholar 

  64. Rosemurgy A, Harris J, Langleben A, et al. Marimastat, a novel matrix metalloproteinase (MMP) inhibitor in patients with advanced carcinoma of the pancreas. 32nd Annual Meeting of the American Society of Clinical Oncology; 1996 May 18–21; clPhiladelphia. Chicago: American Society of Clinical Oncology, 1996: 207

    Google Scholar 

  65. Flynn C, Bull C, Eberwein D, et al. Anti-metastatic activity of BAY 12-9566 in a human colon carcinoma HCT116 orthotopic model [abstract no. 2057]. Proceedings of American Association for Cancer Research; 1998 Jan 24–28: Orlando, FL: 39: 301

    Google Scholar 

  66. Hirte H, Goel R, Major P, et al. Pharmacokinetics of BAY 12-9566: early results of a Canadian Phase I dose escalation study in cancer patients [abstract no. 2484]. Proceedings of American Association for Cancer Research; 1998 Jan 24–28: Orlando, FL: 39: 364

    Google Scholar 

  67. Bull C, Flynn C, Eberwein D, et al. Activity of the biphenyl matrix metalloproteinase inhibitor BAY 12-9566 in murine in vivo models [abstract no. 2062]. Proceedings of American Association for Cancer Research; 1998 Jan 24–28: Orlando, FL: 39: 302

    Google Scholar 

  68. Nozaki S, Sissons S, Casazza AM, et al. Inhibition of human breast cancer regrowth and pulmonary metastases by BAY 12-9566 in athymic mice [abstract no. 2053]. Proceedings of American Association for Cancer Research; 1998 Jan 24–28: Orlando, FL: 39: 301

    Google Scholar 

  69. Levy DE, Ezrin AM. Matrix metalloproteinase inhibitor drugs. In: Emerging drugs, annual executive briefing. London: Ashley Publications Ltd., 1997: 205–30

    Google Scholar 

  70. Santos O, McDermott CD, Daniels RG, et al. Rodent pharmacokinetic and anti-tumor efficacy studies with a series of synthetic inhibitors of matrix metalloproteinases. Clin Exp Metastasis 1997; 15 (5): 499–508

    Article  PubMed  CAS  Google Scholar 

  71. Collier MA, Yuen GJ, Bansal SK, et al. A phase I study of the matrix metalloproteinase inhibitor AG3340 given in single doses to healthy volunteers [abstract no. 1492]. 88th Annual Meeting of the American Association for Cancer Research; 1997 Apr 12–16; San Diego. Philadelphia: American Association for Cancer Research, 1997: 221

    Google Scholar 

  72. Shono T, Ono M, Jimi S, et al. A novel synthetic matrix metalloproteinase inhibitor OPB-3206: Inhibition of tumor growth and metastasis and angiogenesis [abstract no. 3523]. 88th Annual Meeting of the American Association for Cancer Research; 1997 Apr 12–16; San Diego. Philadelphia: American Association for Cancer Research, 1997: 525

  73. Lozonschi L, Sunamura M, Miura K, et al. Matrix metalloproteinases (MMPs), tumor angiogenesis and metastasis related in the treatment outcome with the MMP inhibitor KB 7785 in two murine adenocarcinoma models. Angiogenesis and cancer [abstract no. B2]. Proceedings of an American Association for Cancer Research Special Conference in Cancer Research; 1998 Jan 24–28: Orlando, FL

    Google Scholar 

  74. Miyata S, Fujita S, Shofuda K, et al. Actions of matrix proteinases in in vitro models of angiogenesis: angiogenesis and cancer [abstract no. B14]. Proceedings of an American Association for Cancer Research Special Conference in Cancer Research; 1998 Jan 24–28; Orlando, FL

    Google Scholar 

  75. An Z, Wang X, Willmott N, et al. Conversion of highly malignant colon cancer from an aggressive to a controlled disease by oral administration of a metalloproteinase inhibitor. Clin Exp Metastasis 1997; 15 (2): 184–95

    Article  PubMed  CAS  Google Scholar 

  76. Dupont E, Riviere M, Latreille J, et al. Neovastat: an inhibitor of angiogenesis with anti-cancer activity [abstract no. B37]. Proceedings of an American Association for Cancer Research Special Conference in Cancer Research 1998 Jan 24–28: Orlando, FL

    Google Scholar 

  77. Ries C, Lottspeich F, Dittman KH, et al. HL-60 leukemia cells produce an autocatalytically truncated form of matrix metalloproteinase-9 with impaired sensitivity to inhibition by tissue inhibitors of metalloproteinases. Leukemia 1996; 10 (9): 1520–6

    PubMed  CAS  Google Scholar 

  78. Anderson IC, Shipp MA, Docherty AJP, et al. Combination therapy including a gelatinase inhibitor and cytotoxic agent reduces local invasion and metastasis of murine Lewis lung carcinoma. Cancer Res 1996; 56: 715–8

    CAS  Google Scholar 

  79. Kakeji Y, Teicher BA. Preclinical studies of the combination of angiogenic inhibitors with cytotoxic agents. Invest New Drugs 1997; 15 (1): 39–48

    Article  PubMed  CAS  Google Scholar 

  80. Zucker S, Lysik RM, Zarrabi HM, et al. Plasma assay of matrix metalloproteinases (MMPs) and MMP-inhibitor complexes in cancer: potential use in predicting metastasis and monitoring treatment. Ann NY Acad Sci 1994; 732: 248–62

    Article  PubMed  CAS  Google Scholar 

  81. Zucker S, Lysik RM, Zarrabi MH, et al. Type IV collagenase/ gelatinase (MMP-2) is not increased in plasma of patients with cancer. Cancer Epidemiol Biomarkers Prev 1992; 1: 475–9

    PubMed  CAS  Google Scholar 

  82. Moses MA, Wiederschain D, Loughlin KR, et al. Increased incidence of matrix metalloproteinases in urine of cancer patients. Cancer Res 1998; 58: 1395–9

    PubMed  CAS  Google Scholar 

  83. Delong RK, Miller PS. Inhibition of human collagenase activity by antisense oligonucleoside methylphosphonates. Antisense Nucleic Acid Drug Dev 1996; 6 (4): 273–80

    Article  PubMed  CAS  Google Scholar 

  84. Birkedal-Hansen H, Moore WGI, Bodden MK, et al. Matrix metalloproteinases: a review. Crit Rev Oral Biol Med 1993; 4: 197–250

    PubMed  CAS  Google Scholar 

  85. Belaaouaj A, Shipley JM, Kobayashi DK, et al. Human macrophage metalloelastase: genomic organization, chromosomal location, gene linkage, and tissue-specific expression. J Biol Chem 1995; 270: 14568–75

    Article  PubMed  CAS  Google Scholar 

  86. Messent A, Tuckwell D, Knauper V, et al. Effects of collagenase-cleavage of type I collagen on (alpha)2beta1 integrin-mediated cell adhesion. J Cell Sci 1998; 111 (Pt 8): 1127–35

    PubMed  CAS  Google Scholar 

  87. Freije JM, Diez-Itza I, Balbin M, et al. Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 1994; 269: 16766–73

    PubMed  CAS  Google Scholar 

  88. Cowell S, Knauper V, Stewart ML, et al. Induction of matrix metalloproteinase activation cascades based on membranetype 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3. Biochem J 1998; 15; 331 (Pt 2): 453–8

    Google Scholar 

  89. Okada A, Bellocq JP, Rouyer N, et al. Membrane-type matrix metalloproteinase (MT-MMP) gene is expressed in stromal cells of human colon, breast, and head and neck carcinomas. Proc Natl Acad Sci U S A 1995; 92: 2730–4

    Article  PubMed  CAS  Google Scholar 

  90. Takino T, Sato H, Shinagawa A, et al. Identification of the second membrane-type matrix metalloproteinase (MT-MMP-2) gene from a human placenta cDNA library: MT-MMPs form a unique membrane-type subclass in the MMP family. J Biol Chem 1995; 270: 23013–20

    Article  PubMed  CAS  Google Scholar 

  91. Matsumoto S, Katoh M, Saito S. Identification of soluble type of membrane-type matrix metalloproteinase-3 formed by alternatively spliced mRNA. Biochim Biophys Acta 1997; 1354 (2): 159–70

    Article  PubMed  CAS  Google Scholar 

  92. Puente XS, Pendas AM, Llano E, et al. Molecular cloning of a novel membrane-type matrix metalloproteinase from a human breast carcinoma. Cancer Res 1996; 56 (5): 944–9

    PubMed  CAS  Google Scholar 

  93. Stolow MA, Bauzon DD, Li J, et al. Identification and characterization of a novel collagenase in Xenopus laevis: possible roles during frog development. Mol Biol Cell 1996; 7 (10): 1471–83

    PubMed  CAS  Google Scholar 

  94. Cossins J, Dudgeon TJ, Catlin G, et al. Identification of MMP-18, a putative novel human matrix metalloproteinase. Biochem Biophys Res Commun 1996; 228 (2): 494–8

    Article  PubMed  CAS  Google Scholar 

  95. Pendas AM, Knauper V, Puente XS, et al. Identification and characterization of a novel human matrix metalloproteinase with unique structural characteristics, chromosomal location, and tissue distribution. J Biol Chem 1997; 272 (7): 4281–6

    Article  PubMed  CAS  Google Scholar 

  96. Sedlacek R, Mauch S, Kolb B, et al. Matrix metalloproteinase MMP-19 (RASI-1) is expressed on the surface of activated peripheral blood mononuclear cells and is detected as an autoantigen in rheumatoid arthritis. Immunobiology 1998; 198 (4): 408–23

    Article  PubMed  CAS  Google Scholar 

  97. Bartlett JD, Simmer JP, Xue J, et al. Molecular cloning and mRNA tissue distribution of a novel matrix metalloproteinase isolated from porcine enamel organ. Gene 1996; 183 (1–2): 123–8

    Article  PubMed  CAS  Google Scholar 

  98. Llano E, Pendas AM, Knauper V, et al. Identification and structural and functional characterization of human enamelysin (MMP-20). Biochemistry 1997; 36 (49): 15101–8

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Theradex, 14 Washington Road, Building #3, Princeton Junction, New Jersey, 08550, USA

    Slawomir Wojtowicz-Praga

Authors
  1. Slawomir Wojtowicz-Praga
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wojtowicz-Praga, S. Clinical Potential of Matrix Metalloprotease Inhibitors. Drugs R&D 1, 117–129 (1999). https://doi.org/10.2165/00126839-199901020-00001

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00126839-199901020-00001

Keywords

Search

Navigation