Identifying ligands at orphan GPCRs: current status using structure-based approaches.

摘要: GPCRs are the most successful pharmaceutical targets in history. Nevertheless, pharmacology of many remains inaccessible as their endogenous or exogenous modulators have not been discovered. Tools that explore physiological functions and pharmacological potential these 'orphan' GPCRs, whether they and/or surrogate ligands, therefore paramount importance. Rates receptor deorphanization determined by traditional reverse methods slowed, indicating a need for development more sophisticated efficient ligand screening approaches. Here, we discuss use structure-based discovery approaches to identify small molecule exploring function orphan GPCRs. These studies buoyed growing number GPCR crystal structures solved past decade, providing broad range template homology modelling orphans. This review discusses used establish appropriate signalling assays test activity provides current examples ligands Linked Articles article is part themed section on Molecular Pharmacology G Protein-Coupled Receptors. To view other articles this visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v173.20/issuetoc.