IUPHAR/BPS Guide to PHARMACOLOGY generic slideset

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These slides are provided for public use to facilitate the production of teaching materials and presentations describing the IUPHAR/BPS Guide to PHARMACOLOGY (www.guidetopharmacology.org). The slide set is divided up into sections which can be mixed and matched as required. They are provided under the CC BY license allowing you to adapt and use them for any purpose as long as we are acknowledged as the original authors. The data described herein are current as of December 2014. These slides are also available to download as a Microsoft PowerPoint file at http://www.guidetopharmacology.org/slides/GtoPdb_Generic_Slides.pptx and a PDF at http://www.guidetopharmacology.org/slides/GtoPdb_Generic_Slides.pdf

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IUPHAR Database Meeting

IUPHAR/BPS Guide to PHARMACOLOGY Generic slides for use in presentations and teaching materialsThese slides are provided for public use to facilitate the production of teaching materials and presentations describing the IUPHAR/BPS Guide to PHARMACOLOGY (www.guidetopharmacology.org).The slide set is divided up into sections which can be mixed and matched as required.They are provided under the CC BY license allowing you to adapt and use them for any purpose as long as we are acknowledged as the original authors.The data described herein are current as of December 2014.These slides are available to download as a Microsoft PowerPoint file at http://www.guidetopharmacology.org/slides/GtoPdb_Generic_Slides.pptxand a PDF at http://www.guidetopharmacology.org/slides/GtoPdb_Generic_Slides.pdfThey are also available via slideshare at http://www.slideshare.net/GuidetoPHARM/iupharbps-guide-to-pharmacology-generic-slideset

The IUPHAR/BPS Guide to PHARMACOLOGY (GtoPdb)NameDate, Venuehttp://www.guidetopharmacology.orgwww.guidetopharmacology.orgContentsBackground and history of the databaseAbout NC-IUPHARDatabase content Navigating the website and search toolsRecent additionsThe Concise Guide to PHARMACOLOGYAdditional features and resourcesAcknowledgements

Background and history of the database

Introducing GtoPdb (1)In early 2011 a collaboration was initiated between The International Union of Basic and Clinical Pharmacology (IUPHAR) and the British Pharmacological Society

Aim: to develop a single entry point to information on pharmacological targets and their ligands

Introducing GtoPdb (2)A single entry point to previously separate but complementary information originally contained in the IUPHAR database (IUPHAR-DB) and the Guide to Receptors and Channels (GRAC) series of publications

Remit of GtoPdbGtoPdb aims to:Provide access to data on all known biological targetsMake recommendations on ligands for use in characterising those targetsProvide an entry point into the pharmacological literatureProvide an integrated educational resource with high quality training in the principles of basic and clinical pharmacology and techniquesFoster innovative drug discoveryA brief history of IUPHAR-DBDevelopment of the IUPHAR database of receptors and channels began in 2000Developed by a team of curators, guided by the IUPHAR Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) and its international network of expert subcommitteesIn-depth coverage of the properties and pharmacology of G protein-coupled receptors, voltage- and ligand-gated ion channels, and nuclear hormone receptors.

A brief history of GRACThe Guide to Receptors and Channels (GRAC)Published biennially since 2004 in the British Journal of PharmacologyProvides a rapid overview of the key properties of a wide range of established or potential pharmacological targetsInformation arranged succinctly, so that a newcomer to a particular target group can identify the main elements at a glance.

About NC-iuphar

About NC-IUPHARThe International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug ClassificationObjectives:Issue guidelines for the nomenclature and classification of human biological targetsFacilitate the designation of newly discovered sequences as functional biological targets and potential drug targetsDesignate the polymorphisms and variants which are functionally importantDevelop an authoritative and freely available, global online resource, the Guide to PHARMACOLOGY (http://www.guidetopharmacology.org)NC-IUPHAR expert reviews:Nomenclature articles published in Pharmacological Reviews Articles and editorials on varied topics published in British Journal of PharmacologyCumulative H-Index for NC-IUPHAR is >70.http://www.guidetopharmacology.org/nciuphar.jspNC-IUPHAR membership (1)Core committee:

Outgoing ChairMichael Spedding, FranceVice ChairsAnthony Davenport, UK - Chair Evolving PharmacologyRick Neubig, USA - GPCRsEliot Ohlstein, USA - EditorMembersStephen Alexander, UKThomas Bonner, USAWilliam Catterall, USAArthur Christopoulos, AustraliaJohn Cidlowski, USASir Colin T. Dollery, UKDoriano Fabbro, SwitzerlandKozo Kaibuchi, JapanYoshikatsu Kanai, JapanJohn Peters, UKAlex Phipps, UKJean-Philippe Pin, FranceEx OfficioPatrick du Souich, Canada (Clinical) - IUPHAR PresidentSam Enna, USA - IUPHAR Secretary-GeneralUrs Ruegg, Switzerland - IUPHAR TreasurerSimon Maxwell, UK - Educational Site Project LeaderJamie Davies, UK - Database Principal InvestigatorJoanna Sharman, UK - Database DeveloperAdam Pawson, UK - Senior Database CuratorHelen Benson, UK - Database CuratorElena Faccenda, UK - Database CuratorChristopher Southan, Sweden - Chemical CuratorVeronika Divincova, UK - Project AdministratorElspeth Bruford, UK - representing HGNC

Past Chairs (ex officio)Paul Vanhoutte, ChinaRobert Ruffolo, USANC-IUPHAR membership (2)Corresponding members:

Susan Amara, USAMichel Bouvier, CanadaThomas Burris, USAStephen Charlton, UKMoses Chao, USASteven L. Colletti, USAGraham Collingridge, UKSue Duckles, USARichard Eglen, UKSteven Foord, UKDavid Gloriam, DenmarkGillian Gray, UKDebbie Hay, New ZealandAllyn Howlett, USAFranz Hofmann, GermanyYu Huang, Hong KongAd P. Ijzerman, The NetherlandsMichael F. Jarvis, USABong-Kiun Kaang, KoreaTerry Kenakin, USAJanos Kiss, HungaryStefan Knapp, UKChris Langmead, AustraliaVincent Laudet, France

Margaret (Mandy) MacLean, UKFiona Marshall, UKAlistair Mathie, UKIan McGrath, UKGraeme Milligan, UKStefan Offermanns, GermanyRichard Olsen, USAHelgi Schith, SwedenGraeme Semple, USADavid Searls, USARoland Staal, USABart Staels, FranceGeorg Terstappen, GermanyMary Vore, USA

Clinical Translational Pharmacology Group (core member Sir Colin Dollery)Ed Bullmore, UKRobert Dow, UKGarrett Fitzgerald, USAAlex Phipps, UKPatrick du Souich, CanadaDavid Webb, UKDon Birkett, Australia

NC-IUPHAR subcommitteesNC-IUPHAR Subcommittee Chairs/Liaisons (>90 subcommittees; ~700 scientists)

G protein-coupled receptors Subcommittees5-Hydroxytryptamine: Nick Barnes, John NeumaierAcetylcholine (muscarinic): Arthur ChristopoulosAdenosine: Adriaan Izjermanalpha1-adrenoceptors: Dianne Perezalpha2-adrenoceptors: VACANTAngiotensin: Sadashiva KarnikApelin: Anthony Davenportbeta-adrenoceptors: Terry HbertBile acid: Anthony DavenportBombesin: Robert JensenBradykinin: VACANTCalcitonin: Debbie Hay, David PoynerCalcium-sensing: Ed Brown, Hans Bruner-OsborneCannabinoid: Roger Pertwee, Allyn HowlettChemokine: Philip MurphyCholecystokinin: Laurence MillerComplement peptide: Peter MonkCorticotropin-releasing factor: Richard Hauger, Frank DautzenbergDopamine: Raul GainetdinovEndothelin: Anthony DavenportEstrogen (G protein coupled): VACANTFormylpeptide family: Richard YeFree fatty acid: VACANTFrizzled: Gunnar SchulteGABAB: Bernhard BettlerGalanin: Andrew GundlachGhrelin: Birgitte HolstGlucagon receptor family: Laurence MillerGlycoprotein hormone: Deborah SegaloffGonadotrophin-releasing hormone: Adriaan Ijzerman Histamine: Paul ChazotHydroxycarboxylic acid: Stefan OffermannsKisspeptin: Anthony DavenportLeukotriene: Magnus BckLysophospholipid (LPA): Jerold ChungLysophospholipid (S1P): Sarah SpiegelMelanin-concentrating hormone: Jean-Louis NahonMelanocortin: Tung Fong, Helgi SchithMelatonin: Ralf JockersMetabotropic glutamate: Jean-Philippe PinMotilin: Anthony DavenportNeuromedin U: Gary WillarsNeuropeptide FF/neuropeptide AF: Jean-Marie ZajacNeuropeptide S: Girolamo CalNeuropeptide W/neuropeptide B: Anthony DavenportNeuropeptide Y: Dan LarhammarNeurotensin: Jean MazellaOpioid: Larry TollOrexin: Christopher Winrow P2Y: Geoffrey BurnstockParathyroid hormone: Jean-Pierre VilardagaPeptide P518: Jerome LeprincePlatelet-activating factor: VACANTProkineticin: Philippe Rondard Prolactin-releasing peptide: Helgi SchithProstanoid: Xavier NorelProtease-activated: Nigel BunnettRelaxin family peptide: Roger SummersRelaxin-like: Nick BarkerSomatostatin: Stephan SchulzTachykinin: Susan Leeman, Steven DouglasTrace amine: Janet MaguireThyrotropin-releasing hormone: Marvin GershengornUrotensin: Hubert VaudryVasopressin and oxytocin: Bernard MouillacVIP and PACAP: VACANTLigand-gated ion channels SubcommitteesJohn Peters (Liaison for all LGIC subcommittees)Voltage-gated ion channels SubcommitteesWilliam Catterall (Liaison for all VGIC subcommittees)Nuclear hormone receptors SubcommitteesJohn Cidlowski and Thomas Burris (Liaisons for all NHR subcommittees5-HT3: John PetersGABAA: Richard OlsenGlycine: Joseph LynchIonotropic glutamate: Graham CollingridgeNicotinic acetylcholine: Neil MillarP2X: Charles KennedyZAC: Timothy Hales

Antibodies SubcommitteeAlex Phipps

Adenylyl cyclases SubcommitteeCarmen Dessauer

Drug Target and Chemistry Curation SubcommitteeChristopher Southan

Epigenetics SubcommitteeRabinder PrinjhaCalcium-activated potassium: George GutmanCatSper and Two-Pore: David ChapmanCyclic nucleotide-regulated: Martin BielInwardly rectifying potassium: Yoshihiro KuboTransient Receptor Potential: David ClaphamTwo-P potassium: Steven GoldsteinVoltage-gated calcium: William CatterallVoltage-gated potassium: George GutmanVoltage-gated sodium: William Catterall

Gasotransmitters SubcommitteeAndreas Papapetropoulos and Csaba Szabo

Guanylyl cyclases SubcommitteeAdrian Hobbs and Scott Waldman

Non-coding RNAs SubcommitteeAndrew BakerNHR subcommittees are currently being reformed

Kinases SubcommitteeDoriano Fabbro

Pattern Recognition Receptors SubcommitteeClare Bryant

Proteases SubcommitteeAnthony Turner

Transporters SubcommitteeStephen Alexander

Concise Guide to PHARMACOLOGY EditorsStephen Alexander, John PetersDatabase content

GtoPdb content - targets>2700 established or potential drug targets and related proteins:G protein-coupled receptors (Class A, B, C, frizzled, adhesion and orphan GPCRs)Ligand-gated ion channelsVoltage-gated ion channelsOther ion channelsNuclear hormone receptorsCatalytic receptorsKinasesProteasesOther enzymesTransportersOther protein targets

Target numbers as of December 2014>7200 ligands and drugs:Approved drugsSynthetic organic compoundsMetabolites, hormones, neurotransmittersNatural productsEndogenous peptidesOther peptidesInorganicsAntibodiesLabelled ligands

GtoPdb content - ligands

Ligand numbers as of December 2014Concise target family summariesConcise target family summaries introducing the main properties Expert overviews and commentsGold-standard selective ligands, clinically-used drugs, endogenous ligands and probes (radioligands and PET ligands where available)Further reading lists

Detailed annotation for selected targetsData are collected and reviewed by NC-IUPHAR subcommittees and individual experts:Gene and protein informationIUPHAR nomenclature and synonyms Extensive pharmacology: agonist, antagonist and allosteric regulator affinities, ion channel blockers, enzyme/transporter inhibitors and substratesSignal transduction mechanisms; Tissue distributionFunctional assays; Physiological functionsMouse gene knockout phenotypesClinically-relevant mutations and pathophysiologyGene expression changes in disease; Biologically significant variants

Other featuresExtensively referenced and linked to primary literature in PubMedFocus is on human data but where species differences exist or literature data unavailable other species are givenLinked to corresponding entries in other resources, e.g. UniProt, Ensembl, Entrez Gene, KEGG, OMIM, ChEMBLLigand information including structure, peptide sequences, clinical data and nomenclature, linked up to chemistry resources including PubChem

Navigating the website and search tools

Navigating GtoPdbBrowse lists of targets and ligandsTarget families are listed under expandable family treesTarget information is presented in two levels of detailConcise family summary pagesDetailed pages for selected targetsLigand pages are provided for all compounds in GtoPdbUse the search tools to search by name, keyword, identifier or ligand structure

You may wish to switch to a live demo here. The following slides can be used in place of a demo.22

GtoPdb home page

GtoPdb home page

Histamine receptors family summary page

Histamine H2 receptor concise summary view

Reference information and linkout to PubMed

Link to more details for the H2 receptor

H2 receptor detailed annotation page

Linkouts to other gene and protein resources

Click for species-specific selectivity tableLigand is endogenous in this speciesLigand is labelledLigand is radioactiveApproved drugPrimary target of this compoundInteraction tables

Ligand page for the approved drug ranitidine

Biological activity data for ranitidine at targets in the database

Clinical use and mechanism of action for ranitidinePeptide ligand information

Curated sequence informationPost-translational and chemical group modifications Precursor proteins and encoding genesSimilar sequencesLigand page for the endogenous peptide endothelin-1Bespoke tables for different targetsHeteromeric complexes: subunit compositionGPCRs: signal transduction mechanismIon channels: ion conductance and voltage-dependenceNuclear receptors: DNA co-binding partners, target genesEnzymes: substrates, cofactors, reaction mechanismsTransporters: substrates

GABAB receptor

isopentenyl-diphosphate -isomerase 1Database search functionalityQuick search box at the top of every page with autocomplete for target, family and ligand names

Advanced searches are available on the Target Search and Ligand Search pages

Target search toolsSearch by name or keyword, identifier (e.g. UniProtKB accession) or reference (e.g. PubMed id)

Ligand search toolsSearch by name, identifier (e.g. PubChem CID, InChI) or structure (exact match, similarity, substructure, SMARTS)

Advanced search by keywordKeyword searches, for example by disease name, can facilitate retrieval of associated ligands and targets

A search for Alzheimers disease returns implicated targets and ligands tested in clinical trials

Recent additions

Recent additionsAntibodiesKinasesProteases and hydrolasesEpigenetic targetsInformation on antibodiesCollaboration with IMGT, the international ImMunoGeneTics information system Pharmacological data on 67 approved and experimental therapeutic monoclonal antibodies

Database page for the antibody golimumab43Information on kinasesDatabase pages created for all the human protein kinases and selected lipid kinasesDetailed annotation for the ~30 clinically-used kinase inhibitors, including target affinities, clinical use, and ADME (absorption, distribution, metabolism and excretion) dataPanel data from published screening assays by DiscoveRx, EMD Millipore and Reaction BiologyLinks to the DiscoveRx TREEspot compound profile visualisation tool

lestaurtinib

Imatinib

Information on proteases and hydrolasesMEROPS...