Drug Abuse: Discovering Ligands for Pertinent GPCRs

描述（由申请人提供）： 国家药物滥用研究所（NIDA）的一个重要目标是促进开发治疗和预防吸毒成瘾的新方法。我们的中心将通过为NIDA和NIH研究人员提供有利的资源来促进这一目标，以加速他们的成瘾研究进展，包括但不限于发现和表征新型小分子化合物。我们计划的主要重点领域是以孤儿为代表的基因家族，并确定了七种跨膜G蛋白偶联受体（GPCR）以及烟碱乙酰胆碱受体。在过去的四年里，在我们杜克P30中心的NIDA支持下，我们建立并维护了一个包含几乎所有人类成瘾相关GPCR的开放阅读框架的cDNA集合，更重要的是，NIDA资助的科学家感兴趣的GPCR靶点的现成的基于细胞的测定的扩展库。我们的努力已经与NIH/NIDA的化学家和生物学家在多个其他机构，包括多个项目与分子图书馆探针生产中心网络（MLPCN），导致新的探针化合物的发现KOR，GPRs 33，55，和神经降压素1受体的合作。为了继续我们的使命提供药物治疗的药物成瘾和维持我们的运作在目前的水平，我们正在寻求资金更新作为NIDA P30卓越中心，这将使我们的中心保持在药物成瘾研究的最前沿。我们工作的主要范围将包括使用成瘾模型鉴定和在细胞内和体内表征新型工具化合物。我们的具体目标仍然是开发、维护和提供受体cDNA和细胞测定文库，供NID/VNIH研究人员立即访问，以及时进行筛选。（天数到周周转）我们的合作者提供的受体靶点对有限的库（1000- 5000种化合物）由我们或那些科学家提供;并建立合作项目，旨在发现和表征针对成瘾行为的新型化合物，包括促进这些发现的新测定和技术。这一战略将加快 鉴定临床前化合物以及工具化合物，以表征成瘾生物学，并为药物发现技术的合作科学家提供教育资源。

DESCRIPTION (provided by applicant): An important goal of The National Institute on Drug Abuse (NIDA) is to foster the development of new approaches for drug addiction treatment and prevention. Our Center will advance this objective by providing an enabling resource for NIDA and NIH investigators for accelerating the progress of their addiction research, including but not limited to the discovery and characterization of novel small molecule compounds. The primary areas of focus of our program are the gene families represented by orphan and identified Seven Transmembrane G protein-coupled receptors (GPCRs) as well as nicotinic acetylcholine receptors. With NIDA support of our Duke P30 Center over, the past four years, we have established and maintained a cDNA collection containing the open reading frames for almost all human addiction associated GPCRs, and more importantly an expanding repository of off-the shelf cell-based assays for the GPCR targets of interest to NIDA funded scientists. Our efforts have produced collaborations with NIH/NIDA chemists and biologists at multiple other institutions, including multiple projects with the Molecular Libraries Probe Production Centers Network (MLPCN) that resulted in the discovery of novel probe compounds for the KOR, GPRs 33, 55, and the neurotensin 1 receptor. To continue our mission of providing a pharmacological treatment for drug addiction and maintaining our operation at current levels, we are seeking a renewal of funding as a NIDA P30 Center of Excellence that will enable our Center to remain at the forefront of drug addiction research. The primary scope of our work would include the identification and in cellulo and in vivo characterization of novel tool compounds using addiction models. Our specific aims remain, to develop, maintain, and provide receptor cDNA and cell assay libraries, for immediate access by NID/VNIH investigators, to screen in a timely manner (days to weeks turnaround) the receptor targets provided by our collaborators against limited libraries (1000-5,000 compounds) provided by us or those scientists; and establish collaborative projects aimed towards the discovery and characterization of novel compounds targeting addictive behaviors including the new assays and technologies that will facilitate those discoveries. This strategy will expedite the identification of preclinical compounds as well as tool compounds to characterize the biology of addiction and provide an educational resource for collaborating scientists in drug discovery technology.