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

I-Corps项目的更广泛影响/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许多疾病，例如老年人的神经疾病和阿片类药物成瘾。这个I-Corps项目是基于一种候选药物的发现，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）。一系列对阿片受体和α肾上腺素受体具有激动剂/拮抗剂活性的新配体在体外试验（结合亲和力、微粒体代谢稳定性试验、细胞色素P450抑制、hERG通道抑制和诱导、MDR1-MDCK渗透性、AMES试验、肝细胞稳定性、caco-2渗透性和血浆蛋白/脑组织结合RED）中显示出令人鼓舞的结果，并被证明是治疗疾病、LID和DAO的潜在候选药物。其中阿片受体和肾上腺素受体发挥生物学作用。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。相信该技术是治疗LID和DAO的一种解决方案。该奖项反映了美国国家科学基金会的法定使命，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。

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.