Steroid-binding G-protein-coupled receptors: new drug discovery targets for old ligands.

Steroid-binding receptors have long been a successful target class for the pharmaceutical industry. Clinical applications for steroids range from contraception and hormone replacement therapy to immune regulation and cancer therapy. With the recent demonstration that the orphan GPCR, GPR30 binds and is activated by estrogen, as well as the identification of a GPR30-selective agonist, it is likely that GPR30 represents a novel drug target with many potential clinical applications. This review discusses the role of GPR30 in mediating the effects of estrogen, as well as recent efforts to isolate GPR30-specific ligands using a combination of virtual and biomolecular screening. Finally, comments are made on the future directions regarding GPCRs, steroids and drug discovery.