生物活性

• 描述Marimastat is a broad spectrum MMP inhibitor with IC50 values of 3, 5, 6, 9 and 13 nM for MMP-9, MMP-1, MMP-2, MMP-14 and MMP-7 respectively^[1]. Marimastat is the orally bioavailable analogue of hydroxamate peptidomimetic inhibitor batimastat^[2]. Treatment with 10μM marimastat could inhibit elastin degradation and active MMP-2 production with aortic organ culture^[3]. Marimastat at concentration of 50μg/ml could significantly reduce the invasion of osteosarcoma cells by 30-60%, including U2OS, OHS, and SaOS cells, but not KPDX cells^[4]. Daily administration of marimastat at concentration of 27 mg/kg for 2 weeks by subcutaneously-inoculating mini-osmotic pumps could inhibit peritoneal dissemination of human gastric cancer cells through inhibition of tumor angiogenesis in SCID mice injected with human gastric cancer cells^[5]. Marimastat also works as an inhibitor of TACE (tumor necrosis factor-α converting enzyme). An oral dose of 200mg/kg marimastat almost completely inhibited LPS-induced soluble TNF-α production, but only slightly delayed LPS lethality in mice^[6].
• 作用机制Marimastat is a hydroxamate peptidomimetic compound which can bind covalently to the zinc atom at the MMP-active site.^[2]

• 动物研究
  剂量	Mice: 8.7 mg/kg[7] (subcutaneous osmotic pump), 18 mg/kg[8] (s.c.); 100 mg/kg[9] (p.o.)
  给药途径	OMP (s.c.), p.o.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT00261391	Vascular Anomalies	Phase 1	Completed	-	United States, Massachusetts ... more >> Childrens Hospital Boston, Massachusetts, United States, 02115 Collapse <<
  NCT00002911	Lung Cancer	Phase 3	Completed	-	-
  NCT00003010	Breast Cancer	Phase 3	Completed	-	United States, Arizona ... more >> CCOP - Scottsdale Oncology Program Scottsdale, Arizona, United States, 85259-5404 United States, Illinois Robert H. Lurie Comprehensive Cancer Center, Northwestern University Chicago, Illinois, United States, 60611 CCOP - Carle Cancer Center Urbana, Illinois, United States, 61801 United States, Iowa CCOP - Cedar Rapids Oncology Project Cedar Rapids, Iowa, United States, 52403-1206 CCOP - Iowa Oncology Research Association Des Moines, Iowa, United States, 50309-1016 Siouxland Hematology-Oncology Sioux City, Iowa, United States, 51101-1733 United States, Kansas CCOP - Wichita Wichita, Kansas, United States, 67214-3882 United States, Minnesota CCOP - Duluth Duluth, Minnesota, United States, 55805 Mayo Clinic Cancer Center Rochester, Minnesota, United States, 55905 CentraCare Clinic Saint Cloud, Minnesota, United States, 56303 United States, Nebraska CCOP - Missouri Valley Cancer Consortium Omaha, Nebraska, United States, 68131 United States, New Jersey Trinitas Hospital - Jersey Street Campus Elizabeth, New Jersey, United States, 07201 Hunterdon Regional Cancer Center Flemington, New Jersey, United States, 08822 Hackensack University Medical Center Hackensack, New Jersey, United States, 07601 Morristown Memorial Hospital Morristown, New Jersey, United States, 07962-1956 Riverview Medical Center Red Bank, New Jersey, United States, 07701 St. Francis Medical Center Trenton, New Jersey, United States, 08629 United States, New York Albert Einstein Comprehensive Cancer Center Bronx, New York, United States, 10461 United States, North Dakota Medcenter One Health System Bismarck, North Dakota, United States, 58501 Altru Health Systems Grand Forks, North Dakota, United States, 58201 United States, Ohio CCOP - Columbus Columbus, Ohio, United States, 43206 CCOP - Toledo Community Hospital Oncology Program Toledo, Ohio, United States, 43623-3456 United States, Pennsylvania Hahnemann University Hospital Philadelphia, Pennsylvania, United States, 19102-1192 United States, South Dakota Rapid City Regional Hospital Rapid City, South Dakota, United States, 57709 CCOP - Sioux Community Cancer Consortium Sioux Falls, South Dakota, United States, 57105-1080 Collapse <<

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• 参考文献

• [1] Rasmussen HS, McCann PP, et al. Matrix metalloproteinase inhibition as a novel anticancer strategy: a review with special focus on batimastat and marimastat. Pharmacol Ther. 1997;75(1):69-75.

  [2] Hidalgo M, Eckhardt SG, et al. Development of matrix metalloproteinase inhibitors in cancer therapy. J Natl Cancer Inst. 2001 Feb 7;93(3):178-93.

  [3] Treharne GD, Boyle JR, et al. Marimastat inhibits elastin degradation and matrix metalloproteinase 2 activity in a model of aneurysm disease. Br J Surg. 1999 Aug;86(8):1053-8.

  [4] Bjørnland K, Flatmark K, et al. Matrix metalloproteinases participate in osteosarcoma invasion. J Surg Res. 2005 Aug;127(2):151-6. Epub 2005 Apr 14.

  [5] Wada N, Otani Y, et al. Reduced angiogenesis in peritoneal dissemination of gastric cancer through gelatinase inhibition. Clin Exp Metastasis. 2003;20(5):431-5.

  [6] Tsuji F, Oki K, et al. Differential effects between marimastat, a TNF-alpha converting enzyme inhibitor, and anti-TNF-alpha antibody on murine models for sepsis and arthritis. Cytokine. 2002 Mar 21;17(6):294-300.

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