Utilization of Biased G Protein-Coupled ReceptorSignaling towards Development of Safer andPersonalized Therapeutics.

G protein-coupled receptors (GPCRs) are involved in a wide variety of physiologicalprocesses. Therefore, approximately 40% of currently prescribed drugs have targeted this receptorfamily. Discovery of ß-arrestin mediated signaling and also separability of G protein and b-arrestinsignaling pathways have switched the research focus in the GPCR field towards development ofbiased ligands, which provide engagement of the receptor with a certain effector, thus enrichinga specific signaling pathway. In this review, we summarize possible factors that impact signalingprofiles of GPCRs such as oligomerization, drug treatment, disease conditions, genetic background,etc. along with relevant molecules that can be used to modulate signaling properties of GPCRssuch as allosteric or bitopic ligands, ions, aptamers and pepducins. Moreover, we also discuss theimportance of inclusion of pharmacogenomics and molecular dynamics simulations to achieve aholistic understanding of the relation between genetic background and structure and function ofGPCRs and GPCR-related proteins. Consequently, specific downstream signaling pathways can beenriched while those that bring unwanted side effects can be prevented on a patient-specific basis.This will improve studies that centered on development of safer and personalized therapeutics,thus alleviating the burden on economy and public health.