Johns Hopkins Ion Channel Center

描述（由申请人提供）：离子通道和转运蛋白是对离子、小分子营养物质和代谢物具有选择性渗透性的膜蛋白。这些蛋白质对各种生物过程至关重要，并代表了一大类治疗靶点。生物活性小分子是鉴定改变生命的药物和生命科学发现探针的关键来源。与许多蛋白质类别不同，离子通道和转运蛋白通常需要特殊的仪器和独特的实验专业知识才能进行分析。因此，进行离子通道的大规模化合物库筛选已经提出了相当大的挑战。 约翰霍普金斯化学核心是一个全面运作的，高通量的化合物筛选设施，具有强大的科学优势，运营效率和离子通道专业知识的组合。因此，霍普金斯的现有业务非常适合于为分子库探针生产中心网络（MLPCN）的生产阶段做出贡献。因此，我们建议成立约翰霍普金斯离子通道中心（JHICC）-“专业筛选中心”JHICC将满足以下具体目标：（1）针对NIH指定的五个重要离子通道/转运蛋白靶点中的每一个，筛选30万或更多化合物的大型多样化分子库，（2）积极与其他网络中心的化学家合作，最大限度地开发和生产探针，（3）将结果信息传播到公共领域（PubChem），以及（4）执行中心驱动的研究项目，对分子探针的发现和开发产生重大影响。通过最大限度地提高其质量和生产力，并坚持MLPCN治理机制，JHICC将成为MLPCN和NIH路线图倡议的负责任和高生产力的成员。

DESCRIPTION (provided by applicant): Ion channels and transporters are membrane proteins selectively permeable to ions, small olecular nutrients and metabolites. These proteins are critical to a variety of biological processes and represent a large class of therapeutic targets. Bioactive small molecules are a key source for identification of life-altering Pharmaceuticals and life science discovery probes. Different from many protein classes, ion channels and transporters often require special instruments and unique experimental expertise in order to perform analyses. Thus, carrying out large-scale compound library screens for ion channels has posed a considerable challenge. Johns Hopkins ChemCORE is a fully operational, high throughput compound screening facility with a strong combination of scientific excellence, operational productivity, and ion channel expertise. Hence, the existing operation at Hopkins is ideally suited to contribute the production phase of the Molecular Libraries Probe Production Centers Network (MLPCN). We therefore propose to form the Johns Hopkins Ion Channel Center (JHICC) - "Specialized Screening Center" JHICC will meet the following specific aims: (1) to screen large diverse molecular libraries of 300,000 or more compounds against each of thefive important ion channel/transporter targets assigned by NIH, (2) to actively collaborate with chemists in other network centers to maximize probe development and production, (3) to disseminate the resulting information to the public domain (PubChem), and (4) to perform Center-driven research projects with significant impact on molecular probe discovery and development. By maximizing its quality and productivity and by adhering to MLPCN governance mechanisms, JHICC will be a responsible and highly productive member of the MLPCN and NIH Roadmap Initiative.