Current Pharmaceutical Design - Volume 12, Issue 14, 2006

G protein-coupled receptors (GPCRs) represent the largest known single gene family in the human genome. This superfamily of cell-surface proteins also constitutes the major target for approximately half the medicines on the market today. This issue of Current Pharmaceutical Design focuses on different aspects of the biology and the study of these receptors, with a broad emphasis on how these studies are influencing Read More

Control of cell growth and differentiation has long been a focus of intense research interest, particularly in the context of cancer therapeutics. The evolutionarily-conserved extracellular signal-regulated kinases 1 and 2 (ERK1/2) are serine-threonine kinases that respond to a wide range of mitogens and growth factors to initiate changes in cellular proliferation and differentiation, and are the most important members of the Read More

Seven transmembrane G protein coupled receptors (7TM GPCRs) represent one of the largest gene familes in the human genome. Because of the size of the GPCR family, their proven history of being valuable targets for small molecule drug design, the fact that the absolute number of GPCRs that are targets for current medicines represents only a small fraction of the total encoded by the human genome, and that ligands for Read More

Chemical genomics is a drug discovery strategy that relies heavily on high-throughput screening (HTS) and therefore benefits from functional assay platforms that allow HTS against all relevant genomic targets. Receptor Selection and Amplification Technology (R-SAT™) is a cell-based, high-throughput functional assay where the receptor stimulus is translated into a measurable cellular response through an extensive signalin Read More

Glucagon and the glucagon-like peptides are derived from a common proglucagon precursor, and regulate energy homeostasis through interaction with a family of distinct G protein coupled receptors. Three proglucagon-derived peptides, glucagon, GLP-1, and GLP-2, play important roles in energy intake, absorption, and disposal, as elucidated through studies utilizing peptide antagonists and receptor knockout mice. The ess Read More

The cannabinoid receptors CB1 and CB2 are family A, G-protein Coupled Receptors that mediate the effects of cannabinoids, a class of compounds that are so named because the first members were isolates of the cannabis plant. In recent history, there has been much anecdotal evidence that the potent and diverse physiological responses produced by these compounds can be turned to therapeutic benefit for a wide variety of Read More

Elucidation of protein function is greatly facilitated by the availability of an atomic resolution structure or a reliable molecular model. The difficulty of obtaining atomic resolution structures of membrane proteins in general, and of G-protein coupled receptors (GPCRs) in particular, has made the information available from sequence analysis, mutagenesis, and the literature on related GPCRs exceptionally important. Here, we revie Read More

With the recently completed sequencing and annotation of the human genome, it has become clear that a significant portion of the genome encodes signal-transducing molecules including receptors, protein kinases, ion channels, transporters and coupling proteins. This review focuses on membrane-localized receptors, which represent the largest single group of signal-transducing molecules. Indeed, one can estimate that Read More

The G-protein coupled receptor (GPCR) gene family represents one of the largest families in the mammalian genome. The flexibility of signalling and widespread tissue distribution of these receptors has allowed GPCRs to be employed in the physiological regulation of nearly all biological functions. This, coupled with the fact that it is possible to chemically produce highly specific ligands to these receptors have made GPCR Read More