Abstract
Degradation of basement membrane and extracellular matrix by matrix metalloproteinases (MMPs) is believed to be required for tumor invasion, tumor-induced angiogenesis and vascular invasion. A synthetic hydroxamate, batimastat (also known as BB-94), inhibits MMPs by binding the zinc ion in the active site of the MMP. Batimastat inhibits at least 50% of MMP activity at concentrations less than or equal to 10 ng/ml in vitro. Batimastat retarded ascites accumulation and increased survival in mice with human ovarian tumor xenografts. Acute and long-term toxicological studies revealed no major toxicity in animals. Batimastat is poorly soluble and was administered intraperitoneally (i.p.) as a suspension. Previous studies in patients with malignant ascites have shown no major toxicities at doses as high as 1350 mg/m2.
Publication types
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Clinical Trial
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Clinical Trial, Phase I
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adult
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Aged
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use*
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Collagenases / blood
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Drug Administration Schedule
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Female
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Gelatinases / antagonists & inhibitors*
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Gelatinases / blood
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Humans
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Injections, Intraperitoneal
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Male
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9
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Matrix Metalloproteinase Inhibitors*
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Metalloendopeptidases / antagonists & inhibitors*
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Metalloendopeptidases / blood
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Middle Aged
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Neoplasms / drug therapy*
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Neoplasms / enzymology
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Neoplasms / metabolism
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Phenylalanine / adverse effects
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Phenylalanine / analogs & derivatives*
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Phenylalanine / pharmacokinetics
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Phenylalanine / therapeutic use
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Protease Inhibitors / adverse effects
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Protease Inhibitors / pharmacokinetics
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Protease Inhibitors / therapeutic use*
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Thiophenes / adverse effects
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Thiophenes / pharmacokinetics
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Thiophenes / therapeutic use*
Substances
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Antineoplastic Agents
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Matrix Metalloproteinase Inhibitors
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Protease Inhibitors
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Thiophenes
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Phenylalanine
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batimastat
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Collagenases
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Gelatinases
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Metalloendopeptidases
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Matrix Metalloproteinase 2
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Matrix Metalloproteinase 9