Big Science on a Small Budget: Neuropeptide Receptors and Drug Discovery

Receptors are signal-transducing proteins that sense the cell’s environment and respond to a particular stimulus by eliciting an intracellular response. Due to the importance of their physiological roles, receptors have been major drug targets; they account for about 50-60% of all pharmaceuticals in the market. Hence there is a great interest in identifying new therapeutics by targeting receptors involved in a variety of diseases. Over the last decade, although the amount of money spent towards identifying new drugs has escalated, the number of drugs approved has remained constant. Furthermore, in recent years funding for basic research geared towards the identification of new receptors as targets has continued to decrease both in the public and privatesectors. One approach to carrying out such research during these trying times is to use strategies that maximize publicly available databases and information. For example, data from genomic, proteomic, and metabolomic studies combined with bioinformatics analyses can identify new drug targets. Dynamic collaborations with screening centers for high-throughput screening and/or in silico screening technologies can identify molecules that can serve as tools to evaluate the role of the target in disease as well as leads for drug development. This presentation will describe two examples of these approaches: One example is the identification and characterization of a novel receptor involved in body weight regulation. The other example is the identification of a small molecule that selectively binds to opioid receptor dimers, producing analgesia with reduced side effects.