Novel epoxide hydrolase inhibitor for stroke prevention

用于预防中风的新型环氧化物水解酶抑制剂

• 批准号: 6990653
• 负责人: John D Imig
• 金额: $ 10万
• 依托单位: ARETE THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-30 至 2007-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6990653
• 关键词: arachidonate; blood chemistry; blood pressure; cardiovascular disorder prevention; cardiovascular pharmacology; cerebral artery; cerebral ischemia /hypoxia; drug screening /evaluation; enzyme activity; enzyme inhibitors; epoxide hydrolase; neuroprotectants; nonhuman therapy evaluation; pharmacokinetics; platelet aggregation; spontaneous hypertensive rat; stroke therapy; telemetry; therapy design /development; vascular endothelium

DESCRIPTION (provided by applicant): A major cause of morbidity and mortality is the progression of organ damage associated with cardiovascular diseases. For instance, the incidence of stroke and costs associated with stroke damage continues to have a devastating impact on public health despite numerous treatments aimed at cardiovascular risk factors. Recent findings indicate that increasing levels of epoxides of arachidonic acid (EETs) appear to be new and excellent means to treat cardiovascular diseases. We demonstrated that in vivo inhibition of soluble epoxide hydrolase (SEH) resulted in higher levels of EETs and kidney protection in animal models of hypertension. More recently, we have conducted preliminary studies that suggest that SEH inhibitors can protect the brain from cerebral ischemic damage. Therefore, we will test the hypothesis that SEH inhibitors will have stroke damage protection that is due to decreased cerebral vascular injury and platelet aggregation. First, we will evaluate the ability of a newly developed orally active SEH inhibitor to prevent stroke damage associated with cardiovascular disease. Secondly, we will determine the effect of SEH inhibition on cerebral artery structure, endothelial function and platelet function in stroke-prone spontaneously hypertensive (SHRSP) rats. In the Phase II work, Arete Therapeutics will use the collected information to progress toward clinical trials in the area of stroke and possible new therapeutic avenues.

描述（由申请人提供）：发病率和死亡率的主要原因是与心血管疾病相关的器官损伤的进展。例如，尽管有许多针对心血管危险因素的治疗方法，但与中风损伤相关的中风和成本的发生率仍然对公共卫生产生毁灭性影响。 最近的发现表明，花生四烯酸（EET）的环氧化物水平的增加似乎是治疗心血管疾病的新方法。我们证明，体内抑制可溶性环氧化物水解酶（SEH）在高血压动物模型中导致更高水平的EET和肾脏保护。 最近，我们进行了初步研究，表明SEH抑制剂可以保护大脑免受脑缺血性损害。因此，我们将检验以下假设：SEH抑制剂将具有减少脑血管损伤和血小板聚集的卒中损伤保护。首先，我们将评估新开发的口腔活性SEH抑制剂防止与心血管疾病相关的中风损害的能力。其次，我们将确定SEH抑制对脑动脉结构，内皮功能和血小板功能的影响，自发性高血压（SHRSP）大鼠。在第二阶段的工作中，Arete Therapeutics将使用收集的信息来迈向中风领域的临床试验以及可能的新治疗途径。