PAC1 receptor antagonists as potential treatments for depression and atherosclerosis associated with chronic stress

PAC1 受体拮抗剂作为慢性应激相关抑郁症和动脉粥样硬化的潜在治疗方法

• 批准号: 10916021
• 负责人: Juan Marugan
• 金额: $ 31.01万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10916021
• 关键词: Atherosclerosis; Biological Assay; Biology; Cell Line; Cells; Chronic stress; Collaborations; Disease; Extramural Activities; Follow-Up Studies; Goals; Informatics; Mental Depression; Modeling; Neuroblastoma; PACAPR-1 protein; Pharmaceutical Chemistry; Phenotype; Process; Reporter; Research; Research Personnel; Synthesis Chemistry; Testing; Translations; United States National Institutes of Health; Validation; Work; antagonist; assay development; drug development; drug discovery; high throughput screening; lead optimization; molecular modeling; neuroblastoma cell; new technology; novel; screening; small molecule; small molecule therapeutics; therapeutic development; tool; virtual screening

During this period, a cell-based assay to examine PAC1 activity in neuroblastoma cells was used for high-throughput screening to test approximately 4000 compounds. An additional 200 compounds selected through molecular modeling and virtual screening studies were also tested for ability to antagonize PAC1R. The team has performed follow up studies on a set of the most promising compounds from screening. Additional high-throughput screening utilizing the neuroblastoma reporter cell line is being considered.

在此期间，使用基于细胞的测定来检查神经母细胞瘤细胞中的PAC 1活性，以进行高通量筛选，从而测试约4000种化合物。通过分子建模和虚拟筛选研究选择的另外200种化合物也测试了拮抗PAC1R的能力。该团队对筛选出的一组最有前途的化合物进行了后续研究。 正在考虑利用神经母细胞瘤报告细胞系进行额外的高通量筛选。