A Comprehensive Platform to study drug interaction with physiologically important

研究具有重要生理意义的药物相互作用的综合平台

• 批准号: 8593067
• 负责人: YONG HUANG
• 金额: $ 90.1万
• 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 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8593067
• 关键词: Advanced Development; Adverse effects; Alzheimer' s Disease; Animals; Biological Assay; Cell model; Cells; Central Nervous System Agents; Central Nervous System Diseases; Clinical; Collection; Computer software; Data; Data Set; Databases; Development; Diffuse; Drug Interactions; Drug Prescriptions; Epilepsy; Etiology; Evaluation; Event; Functional disorder; Goals; Human; In Vitro; Inhibitory Concentration 50; Knowledge; Lead; Legal patent; Light; Marketing; Medical; Membrane Transport Proteins; Methods; Molecular Target; Nerve; Neuraxis; Neurotransmitters; Outcome; Parkinson Disease; Peripheral; Pharmaceutical Preparations; Pharmacologic Substance; Pharmacology; Phase; Physiological; Physiological Processes; Physiology; Positioning Attribute; Process; Property; Public Health; Regulation; Research; Research Personnel; Role; Series; Services; Site; Technology; Testing; Therapeutic; Therapeutic Intervention; Validation; Vesicle; Work; assay development; base; data mining; drug development; drug discovery; drug testing; in vivo; inhibitor/antagonist; innovation; interest; neurophysiology; neurotransmission; novel; novel therapeutics; phase 1 study; phase 2 study; public health relevance; receptor; screening; success; therapeutic target; tool; transmission process; uptake

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 the proposed studies is to further the knowledge and available tools to study drug interactions with membrane transporters localized through-out the CNS. Built upon successful Phase I studies, the Phase II studies will result in the most comprehensive collection of CNS transporter assays (25+) commercially available to academic and industrial researchers, removing a critical assay bottleneck in transporter research and CNS drug development. The screening studies (350 CNS and peripherally acting against 20+ key CNS transporters) represent the largest effect to date on in vitro inhibition screen, characterization and in vitro-in vivo extrapolation (IVIVE) of prescription drugs against a panel of key CNS transporters. This innovative approach will provide critical information fundamental to CNS transporter pharmacology, moreover, it could potential lead to discovery of new therapeutic indications for approved drugs.

CNS转运蛋白在神经生理学和病因学中具有重要作用。抑制这些关键转运蛋白 可能在CNS中具有治疗益处或引起严重的副作用。分析平台的开发和 药物对重要的中枢神经系统转运蛋白的抑制作用的综合概况可以产生巨大的影响， 药物发现和开发，例如阐明药物在CNS中的潜在副作用，以及 推进治疗各种中枢神经系统疾病的新药开发，如阿尔茨海默病、帕金森病、 疾病、癫痫等， 拟议研究的总体目标是进一步了解和利用现有工具研究药物 与定位于整个CNS的膜转运蛋白的相互作用。在第一阶段研究成功的基础上， II期研究将产生最全面的CNS转运蛋白测定集（25+） 可供学术和工业研究人员商用，消除了关键的分析瓶颈， 转运蛋白研究和中枢神经系统药物开发。筛选研究（350例CNS和外周作用 针对20+种关键CNS转运蛋白）代表了迄今为止在体外抑制筛选中的最大效应， 针对一组关键CNS的处方药的表征和体外-体内外推（IVIVE） 运输机这种创新的方法将为CNS转运蛋白提供重要的基础信息。 此外，它可能导致发现批准药物的新治疗适应症。