Trends in GPCR drug discovery: new agents, targets and indications.

Hauser AS, Attwood MM, Rask-Andersen M, Schiƶth HB, Gloriam DE

Nat Rev Drug Discov 16 (12) 829-842 [2017-12-00; online 2017-10-27]

G protein-coupled receptors (GPCRs) are the most intensively studied drug targets, mostly due to their substantial involvement in human pathophysiology and their pharmacological tractability. Here, we report an up-to-date analysis of all GPCR drugs and agents in clinical trials, which reveals current trends across molecule types, drug targets and therapeutic indications, including showing that 475 drugs (~34% of all drugs approved by the US Food and Drug Administration (FDA)) act at 108 unique GPCRs. Approximately 321 agents are currently in clinical trials, of which ~20% target 66 potentially novel GPCR targets without an approved drug, and the number of biological drugs, allosteric modulators and biased agonists has increased. The major disease indications for GPCR modulators show a shift towards diabetes, obesity and Alzheimer disease, although several central nervous system disorders are also highly represented. The 224 (56%) non-olfactory GPCRs that have not yet been explored in clinical trials have broad untapped therapeutic potential, particularly in genetic and immune system disorders. Finally, we provide an interactive online resource to analyse and infer trends in GPCR drug discovery.

Affiliated researcher

PubMed 29075003

DOI 10.1038/nrd.2017.178

Crossref 10.1038/nrd.2017.178

pii: nrd.2017.178

Publications 9.5.0