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: 10255278
• 负责人: Juan Marugan
• 金额: $ 30.57万
• 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/10255278
• 关键词: Atherosclerosis; Biological Assay; Biology; Cells; Chronic stress; Collaborations; Communities; Cyclic AMP; Detection; Development; Disease; Extramural Activities; General Population; Goals; Informatics; Mental Depression; Modeling; PACAPR-1 protein; Pharmaceutical Chemistry; Pharmaceutical Preparations; Phenotype; Process; Publications; Reporter; Research; Research Personnel; Resources; Structure-Activity Relationship; Synthesis Chemistry; Translations; United States National Institutes of Health; Validation; Work; assay development; base; drug development; drug discovery; high throughput screening; human disease; improved; lead optimization; new technology; novel; novel therapeutics; screening; small molecule; small molecule therapeutics; therapeutic development; tool

During this period, hits identified in high-throughput screening were assessed for PAC1R antagonism using a cellular reporter of cAMP. Additional cell-based reporter assays are under development to improve detection of PAC1R antagonists and for initiating structure activity-relationship optimization studies. The Early Translation Branch (ETB) has maintained over 130 active collaborations with both NIH and extramural investigators, facilitating drug discovery efforts across the entire spectrum of human disease. These efforts have led to dozens of high-throughput screens and a number of medicinal chemistry campaigns to further improve on screening hits, providing our collaborators and the general research community with publications and a variety of promising small molecule probes and leads. In addition, the ETB has worked to advance a number of informatic initiatives to make better use of existing drug and disease target information and provide the general public with easily accessible resources, further catalyzing the development of new therapies for human disease.

在此期间，使用 cAMP 细胞报告基因评估高通量筛选中鉴定的命中是否具有 PAC1R 拮抗作用。 其他基于细胞的报告测定法正在开发中，以改进 PAC1R 拮抗剂的检测并启动结构活性关系优化研究。 早期翻译分部 (ETB) 与 NIH 和校外研究人员保持着 130 多项积极合作，促进了整个人类疾病谱的药物发现工作。这些努力导致了数十次高通量筛选和许多药物化学活动，以进一步提高筛选命中率，为我们的合作者和一般研究界提供出版物和各种有前途的小分子探针和先导化合物。此外，ETB还致力于推进多项信息化举措，以更好地利用现有药物和疾病靶点信息，为公众提供易于获取的资源，进一步促进人类疾病新疗法的开发。