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：
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
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/8593067
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

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.

中枢神经系统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在中枢神经系统中具有治疗益处或严重副作用。开发测定平台和药物对重要CNS转运蛋白的抑制作用的全面概况可能会产生巨大影响关于药物发现和发育，例如阐明药物在中枢神经系统中的潜在副作用，以及推进开发新药来治疗各种中枢神经系统疾病，例如阿尔茨海默氏病，帕金森氏病疾病，癫痫等，拟议的研究的总体目标是进一步研究药物的知识和可用工具与膜转运蛋白的相互作用局部贯穿中枢神经系统。基于成功的第一阶段研究， II期研究将导致CNS转运蛋白测定最全面的收集（25+）学术和工业研究人员可以商业地使用，取消了关键的测定瓶颈转运蛋白研究和CNS药物开发。筛查研究（350个CNS和外围作用针对20+密钥CNS转运蛋白）是迄今为止在体外抑制筛查中的最大效果，针对密钥中心的面板的处方药的表征和体外体内外推（IVIVE）运输商。这种创新的方法将为CNS运输蛋白提供基础的关键信息此外，药理学，可能会导致发现已批准的药物的新治疗迹象。