Peptide-based therapeutics targeting GPCRs: recent applications in the treatment of metabolic disorders

Abstract

G protein-coupled receptors are among the largest protein superfamilies in the human genome and are responsible for sensing diverse extracellular signals and mediating them into cellular responses. Owing to their broad range of subunits and downstream effectors regulated by specific ligands, these receptors have been appealing pharmacological targets for the discovery of new drugs. Peptide agonists emerged as compelling treatment options for metabolic disorders, and many are currently used in therapy. This perspective comprehensively summarizes the medicinal chemistry efforts over the past 5 years toward the discovery of novel agonists targeting G protein-coupled receptors as promising, life-changing peptide therapies to treat metabolic disorders, like obesity and diabetes.