Nearly 25% of total drug sales and prescriptions are directed at GPCRs, making them the most highly desired drug discovery targets by the pharmaceutical industry and resulting in the development of many of the best-selling drugs on the market today including salmeterol, olanzapine, clopidrogel, losartan, and risperidone. These and other drugs directed at GPCRs are used to treat a variety of disease states affecting the cardiovascular and central nervous systems, gastrointestinal, and metabolic functions, as well as cancer, pain, and allergies. This chapter will review current drugs directed at GPCR targets and describe the process of discovering new GPCR therapeutics including the selection and validation of GPCR drug targets and lead optimization. Additionally, the opportunity for the development of potentially useful therapeutics that may be realized from continued investigation of orphan GPCRs and

GPCR oligomerization will be discussed. The past successes of GPCR-targeted drugs and the future potential of GPCR research suggest that these receptors will continue to be the pharmaceutical industry's prime therapeutic drug discovery targets.

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