G protein-coupled receptors (GPCRs) are among the most intensively studied drug targets, and account for about ~34% of all drugs approved by the FDA. Examples of drugs targeting GPCRs include anti-histamines, β-blockers and ACE inhibitors. In the past, high-throughput methodologies for GPCR screening largely involved the measurement of second messenger production such as Ca2+, cAMP, and inositol phosphate (IP). Over the last decade there have been a number of advances in receptor pharmacology, breakthroughs in structural biology, and innovations in biotechnology, that together have led to several novel strategies to target this important receptor class. For example, since 2014, researchers have harnessed CRISPR technology to knockout (KO) GPCRs, GPCR-associated signaling proteins, or knock-in normal or mutated GPCRs. The panel will discuss some of these approaches including assays that directly quantify receptor coupling to heterotrimeric G proteins and β-arrestin, advancements using rational drug design and AI-based approaches, the increased interest in GPCR-targeting mAbs, and the increased appreciation for the role of pharmacogenomics.
1. Identify some of the challenges to screening GPCRs
2. Describe some of the emerging technologies being used for GPCRs