Drug Abuse: Discovering Ligands for Pertinent GPCRs

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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.