A Comprehensive Platform to study drug interaction with physiologically important

描述：中枢神经系统转运蛋白在神经生理学和病因学中具有重要作用。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。拟定研究的总体目标是进一步了解和使用可用工具研究药物与CNS中膜转运蛋白的相互作用。在成功的I期研究的基础上，II期研究将为学术和工业研究人员提供最全面的CNS转运蛋白测定（25+），消除转运蛋白研究和CNS药物开发中的关键测定瓶颈。筛选研究（350项CNS和外周作用于20多种关键CNS转运蛋白）代表了迄今为止处方药对以下药物的体外抑制筛选、表征和体外-体内外推（IVIVE）的最大效应： 关键中枢神经系统转运蛋白组。这种创新的方法将为CNS转运蛋白药理学提供重要的基础信息，此外，它可能会导致发现新的治疗适应症的批准药物。

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.