Special Issue "GPCR Based Drug Discovery"
QuicklinksA special issue of Pharmaceuticals (ISSN 1424-8247).
Deadline for manuscript submissions: closed (30 November 2010)
Special Issue Editor
Guest Editor
Dr. Sandra Siehler
Novartis Institutes for BioMedical Research, Center for Proteomic Chemistry, WSJ-88.2.05, 4002 Basel, Switzerland
E-Mail:
Interests: G protein-coupled receptors (GPCRs); G proteins; RhoGEF-Rho signaling; adenylyl cyclases; cellular signaling pathways; cell-based/ biochemical/ -physical assays for membrane proteins; cardiovascular pharmacology; drug discovery
Published Papers
Special Issue Information
Multiple G protein-coupled receptors (GPCRs) are present on the cell surface of every cell type, form complexes with other receptors and proteins, and transmit signals into the intracellular lumen to regulate key physiological events. Dysregulated GPCR signaling is causative for pathophysiological conditions, and targeting of GPCRs is hence widely utilized for therapeutic intervention. The recent advancements towards purification, in vitro reconstitution, and structural determination of GPCRs open up new avenues for biochemical –and physical strategies to complement classical cellular drug discovery approaches. Emerging cellular signaling aspects of GPCRs include new temporal and spatial insights, and emerging concepts on G12/13 and MAPK pathways, adenylyl cyclase isoform-specific signaling, and ligand pharmacology. Physiological cell systems containing native GPCRs and signaling environments become more important in early drug discovery to identify GPCR ligands with activities projectable to in vivo disease models and related pharmacodynamic readouts. The purpose of this special issue is to capture these novel facets of GPCR drug discovery.
Dr. Sandra Siehler
Guest Editor
Submission
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed Open Access monthly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 500 CHF (Swiss Francs). English correction and/or formatting fees of 250 CHF (Swiss Francs) will be charged in certain cases for those articles accepted for publication that require extensive additional formatting and/or English corrections.
Keywords
- GPCR structures
- biochemical/-physical approaches for GPCRs
- kinetic analyses of GPCRs signaling
- spatial signaling of GPCRs
- cellular assays for GPCRs in recombinant versus primary cells/ differentiated stem cells
- G12/13 signaling of GPCRs
- GPCR-linked MAPK signaling pathways (ERK, p38MAPK, JNK)
- adenylyl cyclases as mediators of GPCR signaling
- pharmacology/ functional selectivity of GPCR ligands
- pathophysiological signaling of GPCRs
- in vivo pharmacodynamic assays for GPCRs
Planned Papers
Title: Orthosteric Agonists and Allosteric Modulators of Human Calcium-Sensing Receptor: Novel Target for Drug Discovery.
Author: Kausik Ray
Affiliation: Laboratory of Cellular Biology, NIDCD, National Institutes of Health, Bethesda, MD, USA; E-Mail: rayk@mail.nih.gov
Abstract: The human calcium-sensing receptor (hCaR) belongs to the family-C/3 G-protein-coupled receptor (GPCR) superfamily with a uniquely large extracellular amino-terminal ligand-binding domain connected to seven transmembrane helices and an intracellular carboxyl-terminus. The primary physiological function of the hCaR is the maintenance of ionic serum calcium level but this receptor may mediate different function in other tissues. Various divalent and trivalent cations are known as orthosteric agonists and several synthetic allosteric modulators of the hCaR have been identified. These calcimimetics and calcilytics which either increase or decrease the hCaR signaling, respectively, facilitated the understanding of the activation mechanism of this receptor and are of immense therapeutic interest. This review discusses these various agonists and synthetic compounds in hCaR activation and signaling processes and explores the possibility of their roles as therapeutics in various human diseases.
Title: Multiple Facets of cAMP Signaling and Physiological Impact
Author: Martina Schmidt
Affiliation: Centre for Behaviour and Neurosciences (CBN), Faculty of Mathematics and Natural Sciences, University of Groningen, 9713 AV Groningen, The Netherlands; E-Mail: M.Schmidt@rug.nl
Abstract: Chronic degenerative inflammatory diseases, such as chronic obstructive pulmonary disease (COPD), Alzheimer’s dementia and cardiac dysfunctioning, afflict millions of people around the world causing widespread suffering and untold economic loss. Despite the global impact of these diseases, there have been few innovative breakthroughs into their causes, treatment or cures. As with many devastating disorders, chronic degenerative inflammatory diseases are associated with defective or derailed responses to second messengers such as cyclic AMP. Future research efforts may lead to the development of novel drugs for therapeutic interventions in COPD and Alzheimer’s dementia. Importantly to pharmacologist, clinician and biologist, novel cAMP signalling paradigms will provide new insight into both disease processes and new therapeutic approaches aimed at control of inflammation, remodelling, and contraction. In particular, focus will be on Epac - a cyclic AMP-activated guanine nucleotide exchange factor for Ras-like GTPases. Epac has emerged as a novel mediator of pivotal cellular processes, including cellular calcium handling, hypertrophy, integrin-mediated cell adhesion, establishment of cell polarity, cell migration and endothelial barrier functioning. Spatiotemporal dynamics in the subcellular distribution of Epac-driven signalling networks likely determine the net outcome of cyclic AMP signalling in chronic inflammatory disorders.
Last update: 13 April 2011