IUPHAR-DB: new receptors and tools for easy searching and visualization of pharmacological data

Abstract

The IUPHAR database is an established online reference resource for several important classes of human drug targets and related proteins. As well as providing recommended nomenclature, the database integrates information on the chemical, genetic, functional and pathophysiological properties of receptors and ion channels, curated and peer-reviewed from the biomedical literature by a network of experts. The database now includes information on 616 gene products from four superfamilies in human and rodent model organisms: G protein-coupled receptors, voltage- and ligand-gated ion channels and, in a recent update, 49 nuclear hormone receptors (NHRs). New data types for NHRs include details on co-regulators, DNA binding motifs, target genes and 3D structures. Other recent developments include curation of the chemical structures of approximately 2000 ligand molecules, providing electronic descriptors, identifiers, link-outs and calculated molecular properties, all available via enhanced ligand pages. The interface now provides intelligent tools for the visualization and exploration of ligand structure-activity relationships and the structural diversity of compounds active at each target. The database is freely available at http://www.iuphar-db.org.

International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

“…Secondly, by modification of membrane properties or insertion into membranes, lipids can block or reveal the effects of allosteric modulators; membrane interactions can also (Seal et al, 2011). Where the phenotype of the knockout mouse has been published, this is indicated: Further information can be obtained from the IUPHAR Database (http://www.iuphar-db.org/) (Sharman et al, 2011) and the Mouse Genome Database at Mouse Genome Informatics (Eppig et al, 2012 970 drive allosteric changes in receptor conformation and also change the surface charge around channels and receptors. Studies of the crystal structure of the S1P 1 receptor fused to T4 lysozyme in complex with an antagonist sphingolipid mimic have been particularly instructive (Hanson et al, 2012).…”

“…In addition to established transmitter systems, the classification in Pharmacological Reviews (see Foord et al, 2005) and in the IUPHAR Database (IUPHAR-DB) (see Sharman et al, 2011) included "orphan" GPCRs for which the endogenous ligand(s) was not known. Since this publication, considerable progress has been made in screening artificially expressed receptors to identify the cognate endogenous ligand (for example, see Zhang et al, 2011;Civelli, 2012;Yoshida et al, 2012).…”

Molecular aspects of monoamine oxidase B

“…Neurotransmitter release is controlled by signaling pathways and modulated by pre-synaptic auto-receptors. The post-synaptic effect of the neurotransmitters depends on specific families of receptors (D 1-5 5-HT 1-7 and adrenergic receptors, and the related TAAR1 for trace amines), most of which are G-protein coupled receptors (GPCRs) -see (Beaulieu et al, 2015, McCorvy andRoth, 2015), and the IUPHAR database of the genetic and functional properties of receptors (http://www.guidetopharmacology.org/) (Sharman et al, 2011). MAO, as the major metabolic enzyme for the deactivation of the monoamine neurotransmitters, is a key target in neuro-psychopharmacology.…”

Evidence for an interaction of neuronostatin with the orphan G protein-coupled receptor, GPR107

“…Furthermore, neuronostatin signaled via a PKA-dependent mechanism (3), suggesting that the neuronostatin receptor(s) was a G protein-coupled receptor (1,4). Therefore, we hypothesized that the neuronostatin receptor was one of the remaining orphan G protein-coupled receptors, for which the ligand is currently unknown (8,16). We identified by a bioinformatics approach (2) those orphan GPCRs that belonged to receptor families bearing sequence homology to GPCRs that interact with small peptides (3).…”