New Drugs Based on GPCR Agonism and Biased Agonism

G protein-coupled receptors (GPCRs) represent the targets of more than 30% of the drugs currently on the market. However, beneficial effects are most often accompanied by unwanted side effects. Much effort has been invested to better understand the molecular and cellular mechanisms underlying both types of effects in hope to design highly efficacious drugs with reduced or absent side effects. The current most prevalent hypothesis postulates that preferential activation of a given signalling pathway may help reaching this goal. Accordingly, new drugs have been designed and developed in hope to fulfil this criterion. A handful reached the clinics, but the endeavour often proved more complex than anticipated.The goal of this Research Topic is to advance our understanding of biased signalling and to review the current knowledge regarding the causal link with beneficial and unwanted effects. G protein-coupled receptors (GPCRs) are modulating an extremely large number of functions among which pain detection and perception, cognitive and emotional processes or body homeostasis. Accordingly, they are involved in numerous human diseases. We aim to address molecular and cellular mechanisms enabling GPCR biased signalling. This encompasses preferred activation of G protein over beta-arrestin pathways, preferred activation of G protein subunit, or other component of the signalling cascades, allosteric modulation by other membrane or intracellular interactors. We are also interested in drug development, including rationale and strategies underlying the design of biased agonists together with their pharmacological characterisation and the associated preclinical and clinical outcome.The scope of this Research Topic encompasses all G protein-coupled receptors (GPRCs), including but not limited to:• identification of molecular and cellular factors responsible for biased signaling including interaction with other membrane or intracellular factors• design and pharmacological profiling of biased agonists• characterization of activated signaling pathways and resulting behavioral output in preclinical models or in the clinics• concept of biased signaling and biased agonistsThis Research Topic aims to attract high-quality contributions from researchers and experts in the field. We welcome original research articles, narrative reviews, meta-analyses and perspectives that advance our understanding of GPCRs biased signaling at basic and clinical level. Topic editors: Mariana Spetea, Dominique Massotte, Lee-Yuan Liu-Chen Source: https://www.frontiersin.org/research-topics/64841/new-drugs-based-on-gpcr-agonism-and-biased-agonism