Illuminating the understudied GPCR-ome

Abstract

G-protein-coupled receptors (GPCRs) are the target of >30% of approved drugs. Despite their popularity, many of the >800 human GPCRs remain understudied. The Illuminating the Druggable Genome (IDG) project has generated many tools leading to important insights into the function and druggability of these so-called 'dark' receptors. These tools include assays, such as PRESTO-TANGO and TRUPATH, billions of small molecules made available via the ZINC virtual library, solved orphan GPCR structures, GPCR knock-in mice, and more. Together, these tools are illuminating the remaining 'dark' GPCRs.

Keywords: Knock-in mice; cell-based assays; cryo-EM structures; drug discovery; high throughput screening; illuminating the druggable genome (IDG); molecular/chemical probes; nanobody; orphan GPCRs.