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

基本信息

批准号：
8743302
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
项目类别：
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/8743302
关键词：
Advanced Development Adverse effects Alzheimer&apos 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

项目摘要

DESCRIPTION: 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.

描述：CNS转运蛋白在神经生理学和病因学上具有至关重要的作用。抑制这些关键转运蛋白可以具有治疗益处或在中枢神经系统中引起严重的副作用。制定平台的开发以及药物对重要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，例如阐明药物在中枢神经系统中的潜在副作用，并推进新药物的发展来处理各种CNS疾病研究与膜转运蛋白的药物相互作用，贯穿CNS。基于成功的第一阶段研究，第二阶段的研究将导致最全面的CNS转运蛋白测定法（25+）可供学术和工业研究人员商业使用，从而消除了运输蛋白研究和CNS药物开发中的关键测定瓶颈。筛查研究（350个CNS和外周作用于20+关键CNS转运蛋白）是迄今为止对体外抑制筛查，表征和体外体内外推（IVIVE）对A的最大效果。关键CNS转运蛋白的面板。这种创新的方法将为CNS Transporter药理学提供基础的关键信息，此外，它可能可能导致发现批准药物的新治疗迹象。