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Metalloproteinase Inhibitor Marimastat - Crossref

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Last Updated: 07 May 2022

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The matrix metalloproteinase inhibitor marimastat inhibits seizures in a model of kainic acid-induced status epilepticus

a summary of intra-hippocampus injection of kainic acid serves as a model of status epilepticus and temporal lobe epilepsy. MMP-9 contributes to pathological synaptic plasticity that may play a role in the development of an epileptic disorder in reaction to brain insult. The present research found that marimastat can stifle epilepsy development. In vitro, marimastat's inhibitory activity was first demonstrated in neuronal cultures. Next, we investigated marimastat's blood–brain barrier penetration using mass spectrometry and assessed the therapeutic benefits of marimastat against seizure findings. In hippocampal neuronal cell cultures, marimastat restricted the cleavage of nectin-3. marimastat also improved seizure variables, such as seizure score and number, but not necessarily impact status epilepticus. Marimastat's long-term effects were evident up to six weeks after the kainic acid treatment, in which marimastat reduced seizure durations.

Source link: https://doi.org/10.1038/s41598-020-78341-y


Pulmonary delivery of the broad-spectrum matrix metalloproteinase inhibitor marimastat diminishes multiwalled carbon nanotube-induced circulating bioactivity without reducing pulmonary inflammation

We use Marimastat, a broad-spectrum MMP inhibitor, as well as a previously described oropharyngeal aspiration model of MWCNT's administration to investigate the role of MMPs in MWCNT-derived serum peptide formation and endothelial bioactivity. MWCNT research was carried out using either Marimastat or vehicle by oropharyngeal aspiration 1 h before MWCNT's treatment. Independent of MMP blockade, Pulmonary neutrophil infiltration and total bronchoalveolar lavage fluid protein raised. Following MWCNT exposure for key inflammatory indices, the lung cytokine profile was also elevated, with no effect on MMP inhibition. paraphrase fragments of MWCNT-derived serum peptide fragments, which differed peptide compositional profiles, according to MMP blockade's serum peptide fragments. Serum from MWCNT-treated mice triggered inflammation in endothelial cells that had been significantly reduced in serum from Marimastat-treated mice. Conclusions: MWCNT exposure triggered pulmonary inflammation that was largely independent of MMP production, but it did produce circulating bioactive peptides through primarily MMP-dependent pathways.

Source link: https://doi.org/10.1186/s12989-021-00427-w


Phase II Trial of Temozolomide Plus the Matrix Metalloproteinase Inhibitor, Marimastat, in Recurrent and Progressive Glioblastoma Multiforme

Because of laboratory results that metalloproteinases are important in glioma cell transplantation, temozolomide is well tolerated in GBM and is well tolerated, and because of laboratory evidence that metalloproteinases are involved in glioma cell transplantation, the combination of TMZ and the matrix metalloproteinase inhibitor marimastat in patients with recurrent GBM was tested in patients with recurrent GBM. PATIENTS AND METHODS: After standard radiotherapy were introduced, forty-four patients with recurrent GBM were enrolled. TMZ 150 to 200 mg/m 2 days 1 to 5 and MRM 50 mg days 8 to 28 were administered at 28-day intervals for two cycles, followed by patients. Median PFS was 17 weeks, median overall life was 45 weeks, and 12-month PFS was 16%. CONCLUSION: The combination of TMZ and MRM culminated in a PFS at 6 months that exceeded the literature target by 29 percent. This drug combination met phase II study findings, so further research in recurrent patients with GBM may be needed.

Source link: https://doi.org/10.1200/jco.2002.20.5.1383


Phase I trial of Marimastat, a novel matrix metalloproteinase inhibitor, administered orally to patients with advanced lung cancer.

PURPOSE This phase I research was done to investigate the effectiveness and pharmacokinetics of increasing doses of Marimastat in patients with advanced malignancies, as well as determine the phase II recommended dose for use in subsequent studies. PATIENTS AND METHODS In this research, three groups of three patients were treated with increasing doses of the study drug in parallel groups. An additional three patients were added to the highest dose to see if the inflammatory polyarthitis present at that dose level could be minimized by simultaneous administration of nonsteroidal antiinflammatory drugs and/or low-dose corticosteroids. CONCLUSION Marimastat was well absorbed from the gastrointestinal tract, with high amounts of the study drug found in plasma just hours after drug administration. Marimastat plasma concentrations at dose levels 2 and 3 were significantly higher than those required for MMP inhibition in vitro.

Source link: https://doi.org/10.1200/jco.1998.16.6.2150

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions

* Please keep in mind that all text is summarized by machine, we do not bear any responsibility, and you should always check original source before taking any actions