The N-terminal segment and C-terminal segment are, respectively, located in the extracellular and intracellular spaces. The GPCRs are characterized by amino- or N-terminal domain linked to 7 α-helical transmembrane domains (TMDs) and carboxyl or C-terminal domain. The GRAFS classification has five families namely: glutamate, rhodopsin, adhesion, frizzled and secretin. Based on evolutionary homology the GPCR superfamily has been divided into classes and families. The G protein-coupled receptors are a large family of integral membrane proteins with seven transmembrane helices. Currently, numerous diseases involving the endocrine, cardiovascular, neural and immune systems have been effectively treated or managed through the pharmacological modulation of the GPCRs.įull size image Characteristic features of GPCRs , “recent advances in receptor pharmacology, breakthroughs in structural biology and innovations in biotechnology” have all potentiated newer avenues for GPCR drug discovery. Distortion in the signalling pathways or mutations in GPCRs have also been implicated in many diseases. Within the last two decades, there have been significant insights and understanding of G protein-coupled receptors. Additionally, GPCRs are endowed with immense druggable sites that are easily accessed by xenobiotics at the cell surface. This is chiefly because of their ability to regulate numerous and diverse physiological processes including regulation of appetite, taste, smell, inflammation amongst others. They are not surprisingly the largest family of membrane receptors utilized as drug targets both for approved and novel drugs alike. As reported by Oprea and colleagues, there are more than 800 human GPCRs of which more than 400 are non-olfactory. 1) are the most studied membrane receptors in humans as well as numerous other species. This review discusses the recent advances in the molecular pharmacology and future opportunities for targeting GPCRs with a view to drug development. The non-olfactory human GPCRs yet to be clinically explored or tried are endowed with perhaps a huge untapped potential drug discovery especially in the field of immunology and genetics. GPCRs are implicated in a wide variety of diseases including CNS disorders, inflammatory diseases such as rheumatoid arthritis and Crohn’s disease, as well as metabolic disease and cancer. More than 320 therapeutic agents are currently under clinical trials, of which a significant percentage targets novel GPCRs. They have long played a prominent role in drug discovery, such that as of this writing, 481 drugs (about 34% of all FDA-approved drugs) act on GPCRs. GPCRs are regarded as the largest target class of the “druggable genome” representing approximately 19% of the currently available drug targets. Of all drug targets, GPCRs are the most studied, undoubtedly because of their pharmacological tractability and role in the pathophysiology as well as the pathogenesis of human diseases. G protein-coupled receptors (GPCRs) are one of the most important classes of targets for small-molecule drug discovery. Understanding the mechanisms, activated and inhibited pathways as well as other molecular targets involved in existing and emerging disease conditions provides useful insights into their proper diagnosis and treatment and aids drug discovery, development and production.
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