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- W2132621675 abstract "In the present study, we used a comprehensive panel of in vitro assays to evaluate the efficacy and safety of stilbazulenyl nitrone (STAZN) as a lead compound to treat acute ischemic stroke. First, we measured neuroprotection in vitro using two different HT22 hippocampal nerve cell assays. Secondly, to de-risk drug development, we used CeeTox analysis with the H4IIE rat hepatoma cell line to determine the acute toxicity profile of STAZN. Third, STAZN was tested in microsomes from four species for measures of metabolic stability. Last, we determined the Ames test genotoxicity profile of STAZN using Salmonella typhimurium TA989 and TA100. In vitro, STAZN was neuroprotective against toxicity induced by iodoacetic acid, and oxytosis-induced glutathione depletion was initiated by glutamate, with an EC(50) value of 1-5 μM. Secondly, using CeeTox analysis, the estimated C(Tox) value (i.e., sustained concentration expected to produce toxicity in a rat 14-day repeat dose study) for STAZN was calculated to be 260 μM. Third, the half-life of STAZN in humans, dogs, and rats was 60-78 min. Last, the genotoxicity profile showed that STAZN did not induce bacterial colony growth under any conditions tested, indicating the lack of mutagenicity with this compound. STAZN appears to be a multi-target neuroprotective compound that has an excellent safety profile in both the CeeTox and Ames mutagenicity assays. STAZN may have significant potential as a novel neuroprotective agent to treat stroke and should be pursued in clinically relevant embolic stroke models." @default.
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- W2132621675 date "2011-04-05" @default.
- W2132621675 modified "2023-09-25" @default.
- W2132621675 title "De-Risking of Stilbazulenyl Nitrone (STAZN), a Lipophilic Nitrone to Treat Stroke Using a Unique Panel of In Vitro Assays" @default.
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- W2132621675 doi "https://doi.org/10.1007/s12975-011-0071-7" @default.
- W2132621675 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3191534" @default.
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