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（由申请方提供）：发病和死亡的主要原因是心血管疾病相关器官损伤的进展。例如，尽管有许多针对心血管危险因素的治疗方法，但中风的发生率和与中风损害相关的费用继续对公共卫生产生毁灭性影响。 最近的研究结果表明，增加花生四烯酸环氧化物的水平似乎是治疗心血管疾病的新的和优秀的手段。我们证明，在高血压动物模型中，体内抑制可溶性环氧化物水解酶（SEH）导致更高水平的雌二醇和肾脏保护。 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伤。因此，我们将检验SEH抑制剂将具有中风损伤保护的假设，这是由于减少脑血管损伤和血小板聚集。首先，我们将评估一种新开发的口服活性SEH抑制剂预防心血管疾病相关中风损害的能力。其次，我们将研究抑制SEH对易卒中型自发性高血压（SHRSP）大鼠脑动脉结构、内皮功能和血小板功能的影响。在第二阶段的工作中，Arete Therapeutics将利用收集到的信息，在中风领域和可能的新治疗途径方面进行临床试验。