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。抑制这些关键转运蛋白可能会对中枢神经系统产生治疗益处或引起严重的副作用。建立一个分析平台，全面了解药物对重要的中枢神经系统转运体的抑制作用，可以对药物的发现和开发产生巨大的影响，例如阐明药物在中枢神经系统的潜在副作用，并推动新药的开发，以治疗各种中枢神经系统疾病，如阿尔茨海默病、帕金森病、癫痫等。本研究的总体目标是加深对药物与膜转运体相互作用的认识和可用的工具，以深入研究药物与膜转运体之间的相互作用。在第一阶段成功研究的基础上，第二阶段研究将产生最全面的CNS转运蛋白分析(25+)，供学术和工业研究人员商业化使用，消除转运蛋白研究和CNS药物开发中的一个关键分析瓶颈。这些筛选研究(350个CNS和外周作用于20多个关键的CNS转运体)代表了迄今为止在处方药体外抑制筛选、表征和体内外推断(IVE)方面最大的影响。 关键的中枢神经系统运输者小组。这种创新的方法将为中枢神经系统转运体药理学提供关键的基础信息，此外，它还可能导致发现新的已批准药物的治疗适应症。

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.