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Batimastat and Marimastat in Cancer

Summary of Early Clinical Data
  • Henrik S. Rasmussen
Part of the Cancer Drug Discovery and Development book series (CDD&D)

Abstract

Batimastat® and Marimastat® are broad-spectrum matrix metalloproteinase inhibitors (MMPI) with potent activity against most of the major matrix metalloproteinases (MMPs). Batimastat is the prototype MMPI, and is highly active against interstitial collagenase (MMP-1) (IC50 = 3 nM), stomelysin-1 (MMP-3) (IC50 = 20 nM), gelatinase-A (MMP-2) (IC50 = 4 nM), gelatinase-B (MMP-9) (IC50 = 4 nM) and matrilysin (MMP-7) (IC50 = 6 nM) (1). There is also some emerging evidence that Batimastat is a potent inhibitor of MT-MMP (MMP-14) (unpublished observations). The molecular structure of Batimastat is displayed in Fig. 1. Batimastat mimics the substrate of the MMPs, so that the drug works by competitive, potent, but reversible inhibition. Marimastat (Fig. 2) is another broad-spectrum MMPI, with an enzyme inhibitory spectrum very similar to batimastat, but improved pharmacokinetic properties. The only noticeable difference between Marimastat and Batimastat lies in the activity against stromelysin, because Marimastat is a weaker stromelysin inhibitor than Batimastat (IC50 of 230 nM, compared to 20 nM for Batimastat). Whether this weaker activity against stromelysin-1 (MMP-3) has any clinical significance is unclear; however, on theoretical grounds, this would be unlikely, because stromelysin-1 in itself has not been implicated as a significant factor in tumor progression or formation ofnetastases (1). Batimastat and Marimastat are comparable in activity against all other major MMPs.

Keywords

Maximum Tolerate Dose Advanced Pancreatic Cancer Malignant Pleural Effusion Kill Tumor Cell Dose Finding Study 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© Springer Science+Business Media New York 1999

Authors and Affiliations

  • Henrik S. Rasmussen

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