Establishing a comprehensive inhibitory profile of marketed drugs against CNS tra

建立针对 CNS tra 的市售药物的全面抑制谱

• 批准号: 8202244
• 负责人: Juan Jose Fung
• 金额: $ 15万
• 依托单位: OPTIVIA BIOTECHNOLOGY, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-19 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8202244
• 关键词: Establishing; comprehensive; inhibitory; profile; marketed

DESCRIPTION (provided by applicant): CNS Transporters have crucial roles on neurophysiology and etiology. Inhibition of these critical transporters can have therapeutic benefits or cause serious side effects in the CNS. Development of an assay platform and a comprehensive profile of drugs' inhibitory effects on important CNS transporters can have enormous impact on drug discovery and development, such as elucidating drugs' potential side effects in the CNS, and advancing development of new drugs to treat various CNS diseases, such as Alzheimer's disease, Parkinson's diseases, epilepsy etc., The overall goal of this project is to develop a comprehensive assay platform for evaluating drugs' inhibitory effects on key CNS transporters, and then to establish the industry's largest database on inhibitory effects of over 1000 prescription CNS and peripherally acting drugs on these transporters. The initial Phase I work will start with developing assays for 10 crucial CNS transporters, which are known as therapeutic targets or to play critical roles on CNS physiology. A small library of marketed CNS drugs will then be profiled for their inhibitory effects on these transporters, with aims to reveal possible interactions of the drugs with these transporters that are previously unknown to the research community. Future study would extend the scope to developing assays for more than 30 major CNS transporters, and scale up inhibitory profiling efforts for more than 1000 marketed drugs, with aims to explain causes of certain CNS side effects, to reveal potential new therapeutic indications of existing drugs, and to discover potential therapeutic benefits of inhibiting certain key CNS transporters in treating various CNS diseases. PUBLIC HEALTH RELEVANCE: Success of this project would benefit public health enormously through helping inform and mitigate drugs' potential side effects in the CNS, and by helping develop pharmaceuticals to treat various serious CNS disorders, such as Parkinson's disease, Alzheimer's disease, epilepsy etc.. Specifically, the proposed studies will be invaluable for evaluating off-target effects of both CNS and peripherally acting drugs on critical CNS transporters of physiological and/or pharmacological significance, which could potentially lead to discovering new therapeutic indications for marketed CNS drugs, and identifying/validating novel molecular targets for therapeutic intervention.

描述（由申请人提供）：CNS转运蛋白在神经生理学和病因学中具有关键作用。这些关键转运蛋白的抑制可在CNS中具有治疗益处或引起严重副作用。开发分析平台和药物对重要CNS转运蛋白的抑制作用的全面概况可以对药物发现和开发产生巨大影响，例如阐明药物在CNS中的潜在副作用，并促进治疗各种CNS疾病（例如阿尔茨海默病、帕金森病、癫痫等）的新药的开发。本项目的总体目标是开发一个全面的检测平台，用于评估药物对关键CNS转运蛋白的抑制作用，然后建立业界最大的1000多种处方CNS和外周作用药物对这些转运蛋白抑制作用的数据库。最初的I期工作将从开发10种关键CNS转运蛋白的检测方法开始，这些转运蛋白被称为治疗靶点或在CNS生理学上发挥关键作用。然后，将对一个小型的已上市CNS药物库进行分析，以确定其对这些转运蛋白的抑制作用，旨在揭示药物与这些转运蛋白之间可能的相互作用，这些相互作用以前是研究界未知的。未来的研究将扩大范围，开发超过30种主要CNS转运蛋白的检测方法，并扩大1000多种上市药物的抑制性分析工作，旨在解释某些CNS副作用的原因，揭示现有药物的潜在新治疗适应症，并发现抑制某些关键CNS转运蛋白治疗各种CNS疾病的潜在治疗益处。 公共卫生关系：该项目的成功将通过帮助了解和减轻药物在中枢神经系统中的潜在副作用，以及帮助开发治疗各种严重中枢神经系统疾病（如帕金森病，阿尔茨海默病，癫痫等）的药物，极大地造福于公共卫生。具体而言，拟定的研究对于评价CNS和外周作用药物对具有生理学和/或药理学意义的关键CNS转运蛋白的脱靶效应将是非常宝贵的，这可能导致发现市售CNS药物的新治疗适应症，并识别/验证治疗干预的新分子靶点。