Figure 6 shows the structures of the [sPLA.sub.2] inhibitor, varespladib, and other SMT candidates that could be repurposed, the anti-svMP peptidomimetic SMTs, prinomastat, and
marimastat [17,18, 54].
Kubota et al., "Matrix metalloproteinase inhibitor,
marimastat, decreases peritoneal spread of gastric carcinoma in nude mice," Cancer Science, vol.
Over the last few years, antiproteolytic approach in antifibrotic therapies was restricted mainly to matrix metalloproteinases activity; however, broad range MMP inhibitors like
marimastat and prinomastat failed clinical tests, as they led to severe side effects [21, 22].
In a clinical trial, conducted on patients affected by chemotherapy refractory advanced gastric cancer and gastroesophageal cancer, the MMP
marimastat only determined a little difference in survival.
The MMP inhibitors batimastat and
marimastat reduce CNV when applied early in the process [93,94], suggesting a potential therapeutic role for MMP9 inhibitors in AMD.
Hambley, "Studies of a cobalt(III) complex of the MMP inhibitor
marimastat: a potential hypoxia-activated prodrug," Chemistry, vol.
Agents that are MMPs enzyme inhibitors (batimastat,
marimastat) and agents that alter vascular endothelial cells MMPs expression currently are being evaluated as angiostaticagents (16).
Although this design hasproducedpotentinhibitorssuchasBatimastat[11, 12] and
Marimastat [13](Figure 1), none of these MMPIs has successfully completed clinical trials.
The matrix metalloproteinase inhibitor
Marimastat (Tocris Bioscience, Bristol, United Kingdom) was used at 10 [micro]M final concentration.
British Biotech was humbled in the late 1990s when its leading drug hope, a cancer treatment called
Marimastat, failed clinical trials.
A recent trial evaluating the combination of
marimastat (a protease inhibitor) and temozolomide reported a 6-month progression-free survival of 39% compared to 21% with temozolomide alone (Groves et al., 2002).
Once one of the bright lights of the UK sector, it was hit by the failure of cancer drug
Marimastat and pancreatitis treatment Zacutex, both at one point hailed as potential blockbusters.