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GPCRs: The most promiscuous druggable receptor of the mankind
Authors:Khaled Alhosaini  Asim Azhar  Asma Alonazi  F Al-Zoghaibi
Institution:1. Department of Pharmacology & Toxicology, College of Pharmacy, King Saud University, Post Box 2457, Riyadh 11451, Saudi Arabia;2. Interdisciplinary Biotechnology Unit, AMU Aligarh, UP, India;3. Molecular BioMedicine Program, Research Centre, King Faisal Specialist Hospital and Research Centre, P.O.Box: 3354, MBC:03, Riyadh 11211, Saudi Arabia
Abstract:All physiological events in living organisms originated as specific chemical/biochemical signals on the cell surface and transmitted into the cytoplasm. This signal is translated within milliseconds–hours to a specific and unique order required to maintain optimum performance and homeostasis of living organisms. Examples of daily biological functions include neuronal communication and neurotransmission in the process of learning and memory, secretion (hormones, sweat, and saliva), muscle contraction, cellular growth, differentiation and migration during wound healing, and immunity to fight infections. Among the different transducers for such life-dependent signals is the large family of G protein-coupled receptors (GPCRs). GPCRs constitute roughly 800 genes, corresponding to 2% of the human genome. While GPCRs control a plethora of pathophysiological disorders, only approximately one-third of GPCR families have been deorphanized and characterized. Recent drug data show that around 40% of the recommended drugs available in the market target mainly GPCRs. In this review, we presented how such system signals, either through G protein or via other players, independent of G protein, function within the biological system. We also discussed drugs in the market or clinical trials targeting mainly GPCRs in various diseases, including cancer.
Keywords:Arrestin  Drugs  G proteins  GPCR  GRKs  Heterodimerization  Signaling  CCR"}  {"#name":"keyword"  "$":{"id":"k0045"}  "$$":[{"#name":"text"  "_":"Chemokine Receptor  cAMP"}  {"#name":"keyword"  "$":{"id":"k0055"}  "$$":[{"#name":"text"  "_":"cyclic AMP  AC"}  {"#name":"keyword"  "$":{"id":"k0065"}  "$$":[{"#name":"text"  "_":"Adenylyl Cyclase  COX"}  {"#name":"keyword"  "$":{"id":"k0075"}  "$$":[{"#name":"text"  "_":"Cyclooxygenase  DAG"}  {"#name":"keyword"  "$":{"id":"k0085"}  "$$":[{"#name":"text"  "_":"Diacylglycerol  ERK"}  {"#name":"keyword"  "$":{"id":"k0095"}  "$$":[{"#name":"text"  "_":"Extracellular signal-Regulated Kinase  GRKs"}  {"#name":"keyword"  "$":{"id":"k0105"}  "$$":[{"#name":"text"  "_":"G protein-coupled Receptor Kinases  GIP"}  {"#name":"keyword"  "$":{"id":"k0115"}  "$$":[{"#name":"text"  "_":"Gastric Inhibitory Peptide  GLP1R"}  {"#name":"keyword"  "$":{"id":"k0125"}  "$$":[{"#name":"text"  "_":"Glucagon-Like Peptide-1 Receptor  Inositol 1  4  5-triphosphate  PKA"}  {"#name":"keyword"  "$":{"id":"k0145"}  "$$":[{"#name":"text"  "_":"Protein Kinase A  Phosphatidylinositol-4  5-bisphosphate  MAPK"}  {"#name":"keyword"  "$":{"id":"k0165"}  "$$":[{"#name":"text"  "_":"Mitogen-Activated Protein Kinase  NMDA"}  {"#name":"keyword"  "$":{"id":"k0175"}  "$$":[{"#name":"text"  "_":"N-Methyl D-Aspartate  Nbs"}  {"#name":"keyword"  "$":{"id":"k0185"}  "$$":[{"#name":"text"  "_":"Nanobodies  PAR-1"}  {"#name":"keyword"  "$":{"id":"k0195"}  "$$":[{"#name":"text"  "_":"Protease Activated Receptor 1
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