ER beta selective agonist coronary protection--menopause

ERβ选择性激动剂冠状动脉保护--更年期

• 批准号: 6695146
• 负责人: R Kent HERMSMEYER
• 金额: $ 13.38万
• 依托单位: DIMERA, INC.
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-07 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6695146
• 关键词: Macaca mulatta; androstane compound; animal tissue; calcium ion; cardiac myocytes; coronary artery; coronary disorder; drug design /synthesis /production; estrogen receptors; heart disorder chemotherapy; human mortality; postmenopause; serotonin; stimulant /agonist; thromboxanes; topical drug application; vasoconstrictors

DESCRIPTION (provided by applicant): The objective of this Phase I project is to test and develop, using primate coronary artery vascular muscle cells in vitro, a novel estrogen receptor beta (ERbeta) selective (over ERalpha) agonist that is highly effective for protecting coronary arteries against hyperreactivity and also for relieving cardiovascular menopausal symptoms of ovarian steroid deficiency. Such cardiovascular hyperreactivity appears to result from the deficiency of balanced estrogen ERbeta versus ERalpha receptor stimulation after the cessation of ovarian function. This project will examine the effect of the ERbeta Agonist (ERbetaA), which is a natural human steroid metabolite, for the novel indication as a genomic repressor of reactivity in rhesus coronary vascular muscle cell experiments. This project is addressed to the challenge of reduction of coronary dysfunction, disability, and fatalities in menopausal women. Cardiovascular disease, the leading risk of death for women and men over age 50, mechanisms related to declining steroid production and steroid receptor balance are not well understood. The proposed ERbetaA formulation has been designed to significantly improve this situation and enhance quality of life in both women and men. The new commercial product will be a formulation designed to advance the present state by providing the first agent to offer ERbeta selective stimulation. The ERbetaA profile is salutary as it includes protection against coronary hyperreactivity while simultaneously lowering the risk of breast and uterine cancer. Furthermore, the need for only a low concentration of this bioidentical metabolite portends an excellent safety and side-effect prospect. Selective stimulation of ERbeta appears ideal because of this multifaceted protection against coronary hyperreactivity and of breast and uterine carcinomas.

描述（由申请人提供）：本I期项目的目的是使用体外灵长类冠状动脉血管肌细胞测试和开发一种新型雌激素受体β（ER β）选择性（优于ER α）激动剂，该激动剂可高效保护冠状动脉免受高反应性，并可缓解卵巢类固醇缺乏的心血管更年期症状。这种心血管高反应性似乎是由于卵巢功能停止后雌激素ER β与ER α受体刺激平衡不足所致。该项目将检查ER β激动剂（ERbetaA）（一种天然的人类类固醇代谢物）作为恒河猴冠状血管肌细胞实验中反应性基因组抑制剂的新适应症的效果。该项目旨在减少绝经期妇女冠状动脉功能障碍、残疾和死亡的挑战。心血管疾病是50岁以上妇女和男子的主要死亡风险，与类固醇产生下降和类固醇受体平衡有关的机制尚不清楚。拟定的ERbetaA制剂旨在显著改善这种情况，并提高女性和男性的生活质量。新的商业产品将是一种配方，旨在通过提供第一种提供ER β选择性刺激的药物来改善目前的状况。ERbetaA特征是有益的，因为它包括对冠状动脉高反应性的保护，同时降低乳腺癌和子宫癌的风险。此外，仅需要低浓度的这种生物等同代谢物预示着极好的安全性和副作用前景。选择性刺激ER β似乎是理想的，因为这种多方面的保护，对冠状动脉高反应性和乳腺癌和子宫癌。