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Marimastat is an orally-active synthetic hydroxamate with potential antineoplastic activity. Marimastat covalently binds to the zinc(II) ion in the active site of matrix metalloproteinases (MMPs), thereby inhibiting the action of MMPs, inducing extracellular matrix degradation, and inhibiting angiogenesis, tumor growth and invasion, and metastasis. This agent may also inhibit tumor necrosis factor-alpha converting enzyme (TACE), an enzyme involved in tumor necrosis factor alpha (TNF-alpha) production that may play a role in some malignancies as well as in the development of arthritis and sepsis. Check for active clinical trials or closed clinical trials using this agent. (NCI Thesaurus)

Acoording to wikipedia (http://en.wikipedia.org/wiki/Marimastat), Marimastat was a proposed antineoplastic drug developed by British Biotech. It acted as a broad-spectrum matrix metalloproteinase inhibitor. Marimastat performed poorly in clinical trials, and development was terminated.

Current developer:  British Biotech Inc.

  1: van Wijngaarden J, Snoeks TJ, van Beek E, Bloys H, Kaijzel EL, van Hinsbergh VW, Löwik CW. An in vitro model that can distinguish between effects on angiogenesis and on established vasculature: actions of TNP-470, marimastat and the tubulin-binding agent Ang-510. Biochem Biophys Res Commun. 2010 Jan 8;391(2):1161-5. Epub 2009 Dec 14. PubMed PMID: 20004648.

2: Skipper JB, McNally LR, Rosenthal EL, Wang W, Buchsbaum DJ. In vivo efficacy of marimastat and chemoradiation in head and neck cancer xenografts. ORL J Otorhinolaryngol Relat Spec. 2009;71(1):1-5. Epub 2008 Oct 16. PubMed PMID: 18931526; PubMed Central PMCID: PMC2700630.

3: Groves MD, Puduvalli VK, Conrad CA, Gilbert MR, Yung WK, Jaeckle K, Liu V, Hess KR, Aldape KD, Levin VA. Phase II trial of temozolomide plus marimastat for recurrent anaplastic gliomas: a relationship among efficacy, joint toxicity and anticonvulsant status. J Neurooncol. 2006 Oct;80(1):83-90. Epub 2006 Apr 25. PubMed PMID: 16639492.

4: Levin VA, Phuphanich S, Yung WK, Forsyth PA, Maestro RD, Perry JR, Fuller GN, Baillet M. Randomized, double-blind, placebo-controlled trial of marimastat in glioblastoma multiforme patients following surgery and irradiation. J Neurooncol. 2006 Jul;78(3):295-302. Epub 2006 Apr 25. PubMed PMID: 16636750.

5: Zucker S, Wang M, Sparano JA, Gradishar WJ, Ingle JN, Davidson NE; Eastern Cooperative Oncology Group. Plasma matrix metalloproteinases 7 and 9 in patients with metastatic breast cancer treated with marimastat or placebo: Eastern Cooperative Oncology Group trial E2196. Clin Breast Cancer. 2006 Feb;6(6):525-9. PubMed PMID: 16595036.

6: Goffin JR, Anderson IC, Supko JG, Eder JP Jr, Shapiro GI, Lynch TJ, Shipp M, Johnson BE, Skarin AT. Phase I trial of the matrix metalloproteinase inhibitor marimastat combined with carboplatin and paclitaxel in patients with advanced non-small cell lung cancer. Clin Cancer Res. 2005 May 1;11(9):3417-24. PubMed PMID: 15867243.

7: Sparano JA, Bernardo P, Stephenson P, Gradishar WJ, Ingle JN, Zucker S, Davidson NE. Randomized phase III trial of marimastat versus placebo in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy: Eastern Cooperative Oncology Group trial E2196. J Clin Oncol. 2004 Dec 1;22(23):4683-90. Erratum in: J Clin Oncol. 2005 Jan 1;23(1):248. PubMed PMID: 15570070.

8: Jenssen K, Sewald K, Sewald N. Synthesis of marimastat and a marimastat conjugate for affinity chromatography and surface plasmon resonance studies. Bioconjug Chem. 2004 May-Jun;15(3):594-600. PubMed PMID: 15149188.

9: Toppmeyer DL, Gounder M, Much J, Musanti R, Vyas V, Medina M, Orlando T, Pennick M, Lin Y, Shih W, Goodin S, Rubin E. A phase I and pharmacologic study of the combination of marimastat and paclitaxel in patients with advanced malignancy. Med Sci Monit. 2003 Aug;9(8):PI99-104. PubMed PMID: 12942041.

10: Underwood CK, Min D, Lyons JG, Hambley TW. The interaction of metal ions and Marimastat with matrix metalloproteinase 9. J Inorg Biochem. 2003 Jun 1;95(2-3):165-70. PubMed PMID: 12763661.

11: King J, Zhao J, Clingan P, Morris D. Randomised double blind placebo control study of adjuvant treatment with the metalloproteinase inhibitor, Marimastat in patients with inoperable colorectal hepatic metastases: significant survival advantage in patients with musculoskeletal side-effects. Anticancer Res. 2003 Jan-Feb;23(1B):639-45. PubMed PMID: 12680160.

12: North H, King J, Morris DL. Effect of marimastat on serum tumour markers in patients with colorectal cancer. Int J Surg Investig. 2000;2(3):213-7. PubMed PMID: 12678521.

13: Larson DA, Prados M, Lamborn KR, Smith V, Sneed PK, Chang S, Nicholas KM, Wara WM, Devriendt D, Kunwar S, Berger M, McDermott MW. Phase II study of high central dose Gamma Knife radiosurgery and marimastat in patients with recurrent malignant glioma. Int J Radiat Oncol Biol Phys. 2002 Dec 1;54(5):1397-404. PubMed PMID: 12459362.

14: Quirt I, Bodurth A, Lohmann R, Rusthoven J, Belanger K, Young V, Wainman N, Stewar W, Eisenhauer E; National Cancer Institute of Canada Clinical Trials Group. Phase II study of marimastat (BB-2516) in malignant melanoma: a clinical and tumor biopsy study of the National Cancer Institute of Canada Clinical Trials Group. Invest New Drugs. 2002 Nov;20(4):431-7. PubMed PMID: 12448662.

15: Shepherd FA, Giaccone G, Seymour L, Debruyne C, Bezjak A, Hirsh V, Smylie M, Rubin S, Martins H, Lamont A, Krzakowski M, Sadura A, Zee B. Prospective, randomized, double-blind, placebo-controlled trial of marimastat after response to first-line chemotherapy in patients with small-cell lung cancer: a trial of the National Cancer Institute of Canada-Clinical Trials Group and the European Organization for Research and Treatment of Cancer. J Clin Oncol. 2002 Nov 15;20(22):4434-9. PubMed PMID: 12431965.

16: Maekawa K, Sato H, Furukawa M, Yoshizaki T. Inhibition of cervical lymph node metastasis by marimastat (BB-2516) in an orthotopic oral squamous cell carcinoma implantation model. Clin Exp Metastasis. 2002;19(6):513-8. PubMed PMID: 12405288.

17: Miller KD, Gradishar W, Schuchter L, Sparano JA, Cobleigh M, Robert N, Rasmussen H, Sledge GW. A randomized phase II pilot trial of adjuvant marimastat in patients with early-stage breast cancer. Ann Oncol. 2002 Aug;13(8):1220-4. PubMed PMID: 12181245.

18: Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer. 2002 Jul 15;87(2):161-7. PubMed PMID: 12107836; PubMed Central PMCID: PMC2376102.

19: Evans JD, Stark A, Johnson CD, Daniel F, Carmichael J, Buckels J, Imrie CW, Brown P, Neoptolemos JP. A phase II trial of marimastat in advanced pancreatic cancer. Br J Cancer. 2001 Dec 14;85(12):1865-70. PubMed PMID: 11747327; PubMed Central PMCID: PMC2364022.

20: Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA; Marimastat Pancreatic Cancer Study Group. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol. 2001 Aug 1;19(15):3447-55. PubMed PMID: 11481349.

21: Nemunaitis J, Cox J, Hays S, Meyer W, Kebart R, Ognoskie N, Courtney A, Yu Y, Rasmussen H, Tong A. Prognostic role of K-ras in patients with progressive colon cancer who received treatment with Marimastat (BB2516). Cancer Invest. 2000;18(3):185-90. PubMed PMID: 10754986.

22: Tierney GM, Griffin NR, Stuart RC, Kasem H, Lynch KP, Lury JT, Brown PD, Millar AW, Steele RJ, Parsons SL. A pilot study of the safety and effects of the matrix metalloproteinase inhibitor marimastat in gastric cancer. Eur J Cancer. 1999 Apr;35(4):563-8. PubMed PMID: 10492628.

23: Watson SA, Morris TM, Collins HM, Bawden LJ, Hawkins K, Bone EA. Inhibition of tumour growth by marimastat in a human xenograft model of gastric cancer: relationship with levels of circulating CEA. Br J Cancer. 1999 Sep;81(1):19-23. PubMed PMID: 10487607; PubMed Central PMCID: PMC2374341.

24: Nemunaitis J, Poole C, Primrose J, Rosemurgy A, Malfetano J, Brown P, Berrington A, Cornish A, Lynch K, Rasmussen H, Kerr D, Cox D, Millar A. Combined analysis of studies of the effects of the matrix metalloproteinase inhibitor marimastat on serum tumor markers in advanced cancer: selection of a biologically active and tolerable dose for longer-term studies. Clin Cancer Res. 1998 May;4(5):1101-9. PubMed PMID: 9607566.