High Throughput Screening (HTS) in Identification New Ligands and Drugable Targets of G Protein-Coupled Receptors (GPCRs)

Dashan      Wang; Yan      Li; Yugao      Zhang; Yuan      Liu; Guixiu      Shi

doi:10.2174/138620712799218626

Abstract

G protein-coupled receptors (GPCRs) which constitute one of the largest and most versatile families of cell surface receptors are involved in a wide spectrum of physiological functions, such as, neuronal transmission, chemotaxis, pacemaker activity and embryonic development. Therefore, in the past a few years GPCR families have become very important targets in pharmaceutical design. However, according to the human genome project, there are approximately 1000 genes encoding GPCRs, only about 200 of GPCRs have known ligands and functions. Searching for ligands of the unknown GPCRs and better modulators of known GPCRs are currently attracting lots of interest. High throughput screening (HTS), which is commonly defined as an automatic process of testing potential drug candidates efficiently, is widely used in drug discovery. In this review, the use of high throughput screening (HTS) in studying GPCRs and the choice of screening technology in different G-protein signaling pathways were summarized.

Keywords: GPCRs, G proteins, HTS, ligand identification, receptors, physiological functions, GTP binding assays, human genomes, drug discovery, transmembrane receptors, extracellular signals, enzymes, neurotransmitters, hypothalamo-pituitary, hormone, leukocyte, immune cells, nucleotide exchange, glucoprotein, cellular metabolism, allosteric activator, lipid metabolism, lymphocyte migration, autoimmune disease, endogenous ligands