I-Corps: A Lead Candidate for the Treatment of L-DOPA Induced Dyskinesia and Drug Addiction and Overdose

I-Corps：治疗左旋多巴引起的运动障碍、药物成瘾和药物过量的主要候选药物

• 批准号: 1954386
• 负责人: Victor Hruby
• 金额: $ 5万
• 依托单位: University of Arizona
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-02-01 至 2021-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1954386&HistoricalAwards=false
• 关键词: Corps; Lead; Candidate; Treatment; DOPA

The broader impact/commercial potential of this I-Corps project is to help a number of conditions, such as neurological disorders in the elderly and opioid addiction, by providing a potential drug candidate with new chemical properties. This I-Corps project is based on a discovery of a drug candidate for the treatment of L-DOPA Induced Dyskinesia (LID), and Drug Addiction and Overdose (DAO). A new series of ligands with agonist/antagonist activities on opioid receptors and alpha adrenoceptor showed promising in vitro test results (binding affinity, microsomal metabolic stability assay, cytochrome P450 inhibition, hERG channel inhibition & induction, MDR1-MDCK permeability, AMES test, hepatocyte stability, caco-2 permeability, and plasma protein/brain tissue binding RED) and proved to be a potential drug candidate for the treatment of disorders, LID and DAO, where the opioid receptors and alpha adrenoceptor play biological roles. Animal tests studying the effect of HCV-3 on animal models of LID yielded promising results. It is believed that this technology is a solution for the treatment of LID and DAO.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这个I-Corps项目的更广泛的影响/商业潜力是通过提供具有新化学性质的潜在候选药物来帮助一些疾病，例如老年人的神经系统疾病和阿片类药物成瘾。 这个I-Corps项目是基于发现一种用于治疗左旋多巴诱导的运动障碍（LID）和药物成瘾和过量（DAO）的候选药物。对阿片受体和α肾上腺素受体具有激动剂/拮抗剂活性的一系列新配体显示出有希望的体外试验结果（结合亲和力、微粒体代谢稳定性测定、细胞色素P450抑制、hERG通道抑制&诱导、MDR 1-MDCK渗透性、艾姆斯试验、肝细胞稳定性、caco-2渗透性、和血浆蛋白/脑组织结合RED），并被证明是治疗其中阿片受体和α肾上腺素受体发挥生物学作用的疾病LID和DAO的潜在候选药物。 研究HCV-3对LID动物模型影响的动物试验取得了令人鼓舞的结果。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。