Annual Report 2014/15 - IUPHAR/BPS Guide to ?· Good health and luck for 2015 ahead. ... database linking…

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NCIUPHARAnnualReport2014/152BackgroundtoNCIUPHARNCIUPHAR was initiated in 1987 at the Xth International Congress of Pharmacology in Sydney. In 1989, theExecutive Committee of IUPHAR named Paul Vanhoutte (Hong Kong) as chairman of a revised and enlargedcommittee, with Michael Spedding (France) as secretary (1990). This committee energetically expanded itsactivities and the number of subcommittees (to 33), eventually producing the first official compendium on theoccasion of the XIIIth International Congress of Pharmacology in Munich in 1998. Robert Ruffolo (USA) wasChairmanofNCIUPHAR from19982002.MichaelSpeddingbecameChairman in2002andwaselectedagain in2006,andassumedthepostofSecretaryGeneralofIUPHARinJuly2015.NCIUPHARand itspartnersaredevelopingaknowledgeenvironment thatwillenablestudentsandscientists inacademia and industry,working in areas related to pharmacology and drug/target research, to exploit the fullpotentialoftheconsiderableamountof informationondrugactionavailable inthepublishedscientific literature.Thisknowledgeenvironmentwillbeavaluabletoolforbasicandclinicalscientistsseekingnewapproachesfordrugdiscovery research,andthediagnosisandtreatmentofdisease,andavaluableteaching resource forstudentsofpharmacologyandtranslationalmedicine.NCIUPHARhastheobjectivesof:1. Issuingguidelinesforthenomenclatureandclassificationofallthe(human)biologicaltargets,includingallthetargetsofcurrentandfutureprescriptionmedicines2. Facilitating the interfacebetween thediscoveryofnewsequences from theHumanGenomeProjectandthedesignationofthederivedentitiesasfunctionalbiologicaltargetsandpotentialdrugtargets3. Designatingpolymorphismsandvariantswhicharefunctionallyimportant4. Developing an authoritative and freely available, global online resource, originally called the IUPHARdatabase, incollaborationwiththeBritishPharmacologicalSociety(BPS),which isnowaccessibleviatheIUPHAR/BPSGuidetoPHARMACOLOGYwebportal(GtoPdb;http://www.guidetopharmacology.org),witharemitto: provideaccesstodataonallknownbiologicaltargets enablestudentsandscientistsinacademiaandindustry,workinginareasrelatedtopharmacologyanddrug/targetresearch,toexploitthefullpotentialoftheconsiderableamountofinformationondrugactionavailableinthepublishedliterature provideanentrypointintothepharmacologicalliteratureforbasicandclinicalscientistsfromotherdisciplines providean integratededucationalresourcewithaccesstohighqualitytraining intheprinciplesofbasicandclinicalpharmacologyandtechniques fosterinnovativedrugdiscoveryOutgoingChairmansstatement2014/15wasanotheryearofremarkableprogressforNCIUPHARinbuildingourlongtermfoundations,inlinewithourstrategicobjectives.ThankstothealltheattendeesatthetwiceyearlyNCIUPHARmeetings(heldalternativelyinEdinburghandParis), thesemeetingshavebeenscientificallyexciting,administrativelyeffective andkept totime!TheGrantholdersmeetingseverytwomonths(held inEdinburghorbyteleconference)havealsokepttheWellcome Trust grant on track in terms of fulfillment of the aims and objectives for the development ofIUPHAR/BPS Guide to PHARMACOLOGY database (GtoPdb) project in collaboration with the BritishPharmacologicalSociety(BPS).NCIUPHARhasgrowndramaticallyinrecentyears,includingincreasedexpertsubcommittees,andbranchingintonewerareasthatarehavingadramaticimpactondrugdiscoveryandpharmacology.Theimmenserecentgrowthof drug target knowledge, including their crystal structures, has been amajor support to drug discovery. ThisincludesuseofboththeNCIUPHARclassificationsandtheGtoPdb.Weareapproachingthepointofdefiningofnearly allpotentiallydruggable sites encodedby thehumangenome.However,drugdiscovery successhasnotgrownatthesamerateasourknowledgeofdrugtargets.Thisispartlyduetotheexponentiallyincreasingnumberofdrugrelatedvariablesaswellasarapidlyincreasingknowledgeofreceptorpolymorphisms,whichmaybecrucialindiseasestates,andalsocontributetocontroversy.Thehighlightingofthesevariablesviagroupsofexpertshas3beenshowntobeafirststeptowardscontrollingthem. IntheGtoPdb,such identificationandhighlighting istheresultofexpertdrivenanalysisusingour(~90)subcommittees.ThemanagementstructureofNCIUPHARand theGtoPdb team,with input from IUPHARExec,BPS,and inputfromASPET,ASCEPTand the JapanesePharmacologicalSociety,hasbeen functioningextremelywell thus far.However,sinceIhaveassumedthepostofSecretaryGeneralofIUPHAR,itisnowapparentthatthecurrentmodelinvolvingcoordinationbyasingleChairmaybetoodifficultataskintheabsenceof,essentially,afulltimepositiondedicated specifically to that role.Atmy request, a StrategicReviewCommittee (SRC)was established at theOctober2014NCIUPHARmeetingheldinParis,withthetaskofreviewingthecurrentstatusofNCIUPHARanditsactivities, and recommending a path/model for going forward in terms ofmanagement and direction of NCIUPHAR. The SRC is comprised of Doriano Fabbro (Chair), Arthur Christopoulos, Steve Alexander and AdamPawson. An initial report with recommendations has been submitted by the SRC to NCIUPHAR, and furtherdiscussionswilltakeplaceattheAprilmeetinginEdinburgh.TheGtoPdbteamconsistsoffivefulltimestaffwithaparttimeadministrator,thankstotheagreementbetweenIUPHAR,theBPS,theWellcomeTrustandtheUniversityofEdinburgh.Thishasboostedourcapacityasevidencedbytheexpandednumberofsubcommitteeswhichtheyarenowthenexusof.Thedatabaseteamisefficient,highlymotivated,andledbyProfessorJamieDaviesasthedatabasePrincipalInvestigatorattheUniversityofEdinburgh.OurcollaborationwiththeBPShasalsoproducedTheConciseGuidetoPHARMACOLOGY,thesuccessortotheBPSGuidetoReceptorsandChannels(GRAC).ThefirsteditionoftheConciseGuidewaspublishedin2013/14,andwearenowpreparingfortheproductionofthe2015/16editiondueintheautumn.Thiswillbeanupdatedsnapshotoftheconcise target familysummaries in thedatabase,publishedasaseriesofPDFsasdesktop referenceguides.Thispublicationhasbeenamajoreffortofthedatabaseteamandthe ConciseGuideEditors.TheGtoPdbteamhavealsomadesignificantimprovementsandenhancementstothewebinterfaceanddatabase,whicharedetailedinthisreport.Last July,NCIUPHARwas extremelywell represented atWCP2014 in Cape Townwith 7members presentinginspiredplenarylectures,and14membersspeakingineightsymposia.Thiswasafabulousscientificmeetingwithexcellent organization. We now look forward to WCP2018 in Kyoto (congratulations to the JapanesePharmacologicalSocietyonsecuringthis!)andWCP2022inGlasgow(congratulationstotheBPSonsecuringthis!).Goodhealthandluckfor2015ahead.MichaelSpeddingOutgoingChairmanofNCIUPHARSecretaryGeneralofIUPHARCurrentandfuturedirectionsforNCIUPHARNCIUPHAR isperhapsthemostpublicsuccessof IUPHAR,and isengaged inamajortask;todefineallthemaindrugtargetsencodedbythehumangenome,andannotatetheminadatabasefreelyaccessibleworldwideand,importantly,linkthemtotherapeuticsandpharmacologicaltargetvalidation.Majoreffortscontinuetodefinethemainvariablesindrug/receptorinteractionsincludingtheparametersthatcanlead to variation in receptor function and pharmacology (i.e. biased signalling, splice variation, receptorpolymorphisms,heterooligomerisation,allostericmodulation,posttranslationalmodification,epigenetictargets,noncodingRNAs,andlinkagetomultiplesignallingcascades).Theseareasareofgreatinterestbecausetheymayconsiderablyexpandtherepertoireofpotentialtargetsfordrugdevelopment,andareunderevaluationbyworkinggroups, which will lead to a number of reports about issueswhichareofcrucial importanceforpharmacology.All theseareashavebeenorwillbeworkedon for relevance forpharmacology,andadditionallymaybeuseful4fundingapplicationareastoensurethefuturesustainabilityofNCIUPHARactivities,andtheGtoPdbproject.The immense recentgrowthofknowledgeaboutdrug targets,with their crystal structures,hashad adramaticimpact on drug discovery and pharmacology, and importantly, NCIUPHAR classifications have been widelyadopted.Inthepastyear,wehavemadegreatstridestoproactively includenewdrugtargets intheGtoPdb,andrecruitexperts toadviseon them; todatewehave>2700annotatedprotein targets in theGtoPdb,with>7500ligands,includingallapproveddrugs(~1200).There is growing research interest, academically, clinically and industrially, in the pharmacology of immunity,inflammationand infection indefiningthe immunological/inflammatorytargets indiseasestates,withtheirmainpharmacology.Withintheresearchcommunity,there isanurgentneedforaprecompetitive,unbiasedresourcethat will integrate highlevel expertise in immunity, inflammation and infection, pharmacology andmedicinalchemistry.Atpresent, immunologicalandpharmacologicalknowledgeareheldbyseparatecommunitiesandthebestresourcesfallshortofwhat isneeded.GtoPdb isthebestmolecularpharmacologydatabase,but iscurrentlylimited in the immunity, inflammationand infectionarea.Wehaveapplied totheWellcomeTrust for funding toextendGtoPdbintothisarena,andtoproduceaGuidetoIMMUNOPHARMACOLOGY.Wehavealsoapplied for funding foraCOSTAction inneuropharmacology/neuroimmunology.This ispartlyasaresultofourcollaborationwiththeEuropeanCollegeofNeuropsychopharmacology (ECNP)andmembersoftheNomenclatureTaskForce fordrugs inpsychiatry.There isa longway togobut,asa firststrategic step,wearecollatingthedrugsindevelopmentforAlzheimersandseveralexamples(inconjunctionwithECNP)inpsychiatry,datatrawling,andlinkingwithexpertsubcommittees.Thus,wewouldnotonlybeabletoregrouptargetsbytype,butalsobytherapeuticindication.Thiswouldbeofgreatusetopatientgroups.Anexcitingchallengeon thenot toodistanthorizon isour 'OneHealth' Initiative;OneBiology,OneHealth,OneMedicine:An IntegratedDatabaseforthePharmacologicalActionofDrugs inHumans,DomesticAnimalsandModelOrganisms.WewillbesubmittinganapplicationtotheBBSRCforfundingtodrivethisinitiativeinduecourse.Weare moving towards encouraging our subcommittees of experts to include information on translationalpharmacology on drug targets.Wewill also be extendingGtoPdb into the area of stem cell pharmacology (adatabase linkingstemcellsciencewithexpertlycuratedpharmacologicalknowledge),andalso into thecriticallyimportantarenaofenvironmentalpharmacology(adatabasethatprovidescomprehensiveinformationondefinedandemergingpesticiderisks,includingtheiraffinitiesandpotencyinidentifiedspecies).However,giventhecurrentbudgetaryclimate(seeAppendixV:Fundsavailableasof31stMarch2015**),thisisallreliantonfunding,whichwearevigorouslypursuing.Finally,workingwith theUniversityofEdinburghDrupalWebsiteService,andwith funding fromASPET,SimonMaxwellhasspearheadedthedevelopmentoftheIUPHAR/ASPETPharmacologyEducationProject,aneducationportalthatwillbecloselylinkedwiththeGtoPdb.Itwillprovideaccesstohighqualitytrainingintheprinciplesandtechniquesofbasicandclinicalpharmacology.OrganisationofNCIUPHARCorecommitteeThecorecommitteeofNCIUPHARislistedinAppendixI.ThebiannualcoreNCIUPHARmeetingsarethemedandwehaveestablishedanalliancewiththeJapanesePharmacologySocietywhopaythetravelfortwomembers*,butwhoareinvitedaccordingtothemeetingthemes.CorrespondingMembersInordertobroadentheexpertiseofthecorecommittee,thenumberofcorrespondingmembers(seeAppendix I)hasbeen further increased, to include7newmembers:DavidGloriam (UniversityofCopenhagenandGPCRDB,Denmark),GillianGray(UniversityofEdinburgh,UK),BongKiunKaang(SeoulNationalUniversity,Korea),StefanKnapp (Structural Genomics Consortium, UK),Margaret (Mandy)MacLean (University of Glasgow, UK), FionaMarshall (Heptares, UK) and Georg Terstappen (AbbVie, Germany). Corresponding members attend selectedmeetingsofNCIUPHAR and are invited according to themeeting themes.They include representativesof themajorpharmaceuticalcompanies.5EvolvingPharmacologyGroupAnthonyDavenport leadsagroupwhichmonitorsthe deorphanisationofGPCRsandevolvingpharmacologyofdrugtargets ingeneral.Particularly importantandtimelybreakthroughsare included intheHotTopicssectionofthedatabasealongwithemailalerts.ClinicalTranslationalPharmacologyGroupInordertoprovideadviceonthetranslationalaspectsofdrugtargetpharmacology,asubgroup(seeAppendixI)ofclinicalpharmacologists(coremember,SirColinDollery)discusshowbesttorespondtothewishesofourclinicalcolleaguesandtotranslateactivityatdrugtargetsitestoclinicalefficacy.SubcommitteesChairpersons(seeAppendixII)proposealistofexperts,ratifiedbyNCIUPHAR,toensureadequaterepresentationof the field. The chairperson of each subcommittee plays a critical role coordinating the actions of thesubcommittee, organising meetings, finalising documents and the website pages. However, we encouragepostdocstojointhesubcommittee,aschairssimplydonothaveenoughtimetofillinthevarioustemplatefieldspostdocscanthereforegetpublicationcredits,andseveralNCIUPHARpublicationshavebecomecitationclassics.ThehindexofNCIUPHARis>74.Thesubcommitteesmeettoestablishconsensusonclassification,andtoensurethattheNCIUPHARguidelinesare compliedwith.Wenowhavemore>90subcommittees(seeAppendixII).PublicationsandOutreachRecentpublicationsNCIUPHAR has built its reputation on the basis of its published articleswith nomenclature recommendationswhichareadoptedworldwide.NCIUPHARhasanhIndexof74 forarticleswhichcarry thebadge IUPHAR.NCIUPHAR has a longstanding, formal collaboration with ASPET and Pharmacological Reviews, and the officialnomenclature reports are published in the journal. In addition, our collaborationwith the BPS has led to thepublication of a series of general stateofthefield review articles (alongside database updates) in the BritishJournalofPharmacology.EightNCIUPHARnomenclaturereports(seeAppendixIII)haveappearedinPharmacologicalReviews(Editor,EliotOhlstein) so far during the 2014/15 period, reflecting the activity of NCIUPHAR. In addition, 12 NCIUPHARcommissioned reviews for theBritish JournalofPharmacology (EditorinChief, IanMcGrath)have recentlybeenaccepted(seeAppendixIII).Duringthesecondhalfof2014,AdamPawsonandthePressEditorsattheBritishJournalofPharmacologystartedimplementing links directly from all published review articles (starting initially with the IUPHAR reviews) andresearch articles toGtoPdb entries.All articles (since ~August 2014) now include a Table of links beneath theabstractlistingalltargetsandligandsinthearticlewithhyperlinkstothecorrespondingentriesintheGtoPdb,thusallowingreadersinstantaccesstothewealthofinformationcontainedinthedatabase.NewsletterThebiannualNCIUPHARnewslettercontinuestobedistributed inthespringandautumn,throughamailing list(usingMailChimp EmailMarketingandEmailListManagersoftware)comprisingall IUPHARmembersocieties,NCIUPHAR subcommittees and collaborators, pharmacology departmentsworldwide, and database userswhohave signedup to receive news alerts; and wasmade available for download from GtoPdb homepages. ThenewsletterwasalsoadvertisedonsocialmediaandtheRSSfeed.GtoPdbteamrepresentationofNCIUPHARatconferencesandmeetingsTheactivitiesofNCIUPHARhavebeenpromotedbyNCIUPHARrepresentativesatthefollowingconferencesandmeetingsduringthepastyear: The7th InternationalBiocurationConference (InternationalSociety forBiocuration),Toronto,April2014;HelenBenson ComputationalChallengesinDataCitationworkshop,Philadelphia,April2014;JoannaSharman;6 The GLISTEN Barcelona GPCR Spring Conference 2014, GPCRDB SatelliteWorkshop, Barcelona, April2014;JoannaSharman BioITWorld,Boston,April2014;ChristopherSouthan Presentation at the Department of Drug Design and Pharmacology, Faculty of Health And MedicalSciences,UniversityofCopenhagen,May2014;ChristopherSouthan SULSASyntheticBiologyMeeting,Edinburgh,June2014;AdamPawsonandJamieDavis International Conference on Chemical Structures (ICCS/GCC), June 2014,Noordwijkerhout; ChristopherSouthan WorldCongressofPharmacology2014,CapeTown,SouthAfrica,July2014;AdamPawsonandChristopherSouthan Quantitative nutrition and metabolism, University of Reading; Contacts made include Marcus Tindall(Reading)whoissettingupaconsortiumonsystemspharmacology,September2014;HelenBenson Webservicesworkshop;Nijmegen,TheNetherlands,September2014;JoannaSharman GLISTEN/GPCRDBBudapest2014Conference,Budapest,October2014;AdamPawson ClinicalGenomesScotlandMeeting,Edinburgh,October2014;JoannaSharman Pharmacology 4th year honours tutorial session on databases and GtPdb demo, October 2014; HelenBensonandElenaFaccenda RSCCICAGWhat'sinaNamemeeting,RSC,London,October2014;ElenaFaccenda BPSPharmacology2014meeting,London,December2014 88thAnnualMeetingoftheJapanesePharmacologicalSociety,Nagoya,March2015;AdamPawson Inaddition,wehavealsohadrepresentationatmanyothermeetingbymembersofNCIUPHARUpcoming: BNA2015:FestivalofNeuroscience,Edinburgh,April2015;AdamPawson,HelenBenson,ElenaFaccenda BPSFocusedMeeting,April2015,Edinburgh,GtoPdbteam JointASCEPTBPSScientificMeeting,HongKong,May2015;AdamPawson 23rdAnnualInternationalConferenceonIntelligentSystemsforMolecularBiologyandthe14thEuropeanConferenceonComputationalBiology,Dublin,July2015;JoannaSharman AmericanChemicalSocietyMeeting,Boston,August2015;ChristopherSouthan Inaddition,wewillalsohave representationatExperimentalBiology2015 (SanDiego),Physiology2015(London),andothersthankstoourpartnershipwithBPSSocialmediaandWikipediaWeusesocialmediasitestofurthertheoutreachofGtoPdb,andtokeepexistingusersupdated. Facebook:Thesepagesareupdatedwith regular features,databasenewsand links topaperson topicsrelevanttothedatabasecontent.Facebookusersareableto Likethedatabasesandtheindividualitemspostedbythecurators.Wecurrentlyhave>2900likes Twitter:UpdatestoourfeedsincludeaataglanceversionoftheregularfeaturesonourFacebookpages,retweetsofitemspostedbyour>580followersandTwitteruserswefollow,andtweetsaboutkeypapersFollowing various other databases, publications, suppliers and individuals working in the fields ofpharmacologyandbioinformaticsisausefulmarketingtoolforthedatabases(sopleasefollowus). LinkedIN: The Curation Team and Committee Chairs have increased their reciprocal connectivity over2014/15andhave thereby significantlyextended the collective internetworkoutreach forpostingmajorupdates Blogging: The guidetopharmacology blog (http://blog.guidetopharmacology.org/) allows the databaseteamtosharefeaturedevelopments,technicalupdates, articlesoreventsatagreater levelofdetailandcrosslinkingthanshorterpostingstypicaloftheotherthreenetworks(guestpostsarewelcome) Slideshare:TheSlideshareaccount(http://www.slideshare.net/GuidetoPHARM)allowsthedatabaseteamtoshareslidesetsandposterswiththecommunity.Thesiteallowsuserstofindrelatedcontentbytopic.Ourslidesareprovingtobepopularwithover600viewssofar Wikipedia:TheWikipediapages forGtoPdbare regularlyupdated,andweare in constant contactwith7WikipediatoensurethatlinksfromtheirligandandtargetspagespointtoGtoPdbRecentGtoPdbwebinterfaceanddatabasedevelopmentsBackgroundThe IUPHAR/BPSGuide toPHARMACOLOGY (GtoPdb;http://www.guidetopharmacology.org) isanopenaccessdatabaseprovidingpharmacological,chemical,genetic, functionalandpathophysiologicaldataon the targetsofdrugs.Itincludesliteraturederived,quantitativedataontheactionsofapprovedandexperimentalcompoundsattheirtargets.GtoPdbaimstoprovideconciseoverviewsofthekeypropertiesofawiderangeofestablishedandpotentialdrugtargets,withnomenclatureinformation,selectiveligandsandbackgroundreading.Developedunderthe auspices of the International Union of Basic and Clinical Pharmacology (IUPHAR) and the BritishPharmacological Society (BPS), the data are curated by an international network of >650 expert contributorscoordinatedbythe IUPHARNomenclatureCommittee(NCIUPHAR).GtoPdb includesdataon>2700targetsandtheirinteractionswithligands.Targetsaredividedintofamiliesandtheinformationissummarisedonasinglepage.Moredetailedinformationanddruglistsareprovidedforasubsetofimportanttargets.Thedataarelinkedtootherdatabases, includingEntrez,UniProt,ChEMBL,DrugBank,PubChemand referencecitations inPubMed.Eachofthe>7500 smallmoleculeandpeptide ligands ismanuallyannotatedwith2D chemical structuresoraminoacidsequences, nomenclature and clinical information for approved drugs. The Concise Guide to PHARMACOLOGY(http://www.guidetopharmacology.org/concise) is abiennial publication snapshotof thedatabasewith the keypropertiesofeachtargetfamily,intendedasaquickdesktopreferenceguide.Currentworkincludescompletingtheannotationofall the targetsof currentlyapproveddrugs,aswellas those indevelopmentand the likely futurecandidatetargets.Withfuturefunding,theintentionistoexpandintotheareasofimmunopharmacology,stemcellpharmacology and environmental pharmacology. Educational resources to guide scientists and students inpharmacological principles and techniques are also being developed. GtoPdb is run by one fulltime databasedeveloper, four fulltime curatorsandoneparttimeprojectadministrator,with joint funding from IUPHARandBPS,andathreeyeargrantfromTheWellcomeTrust(initiated inNovember2012).TheGtoPdbteamare ledbyProfessorJamieDaviesasthedatabasePrincipalInvestigatorattheUniversityofEdinburgh.Ourlongtermaimsaretoprovide: an authoritative synopsis of the complete landscape of current and research drug targets, providingquantitativepharmacological informationonallof the (human) targetsofcurrentprescriptionmedicinesandotherlikelytargetsoffuturesmallmoleculedrugs anaccuratesourceofinformationonthebasicscienceunderlyingdrugaction,andrigorouscurationofthestructuresandnomenclatureofthechemicalsubstancesintheresource,sharedandrefinedincollaborationwithotherdatabases,includingChEMBL,ChemSpider,DrugBankandPubChemwithwhomwehavestrongties guidancetoresearchersinselectingappropriatecompoundsforinvitroandinvivoexperiments,includingcommerciallyavailablepharmacologicaltoolsforeachtarget informationonclinicallyuseddrugs in the resource (e.g.approvaldate,ADME,molecularmechanismofaction,summaryofclinicaluse) an integratededucationalresourceforresearchers,studentsandthe interestedpublic(oursistersite,theIUPHAR/ASPETPharmacologyEducationProjectdevelopedwithseedfundingprovidedbyASPET)Recentdevelopments1. Newfeaturesofthewebinterfaceanddatabase: Thedatasupportedprimarytargetsofdrugsareindicatedwithanewsymbol NewSpecialistdatabasessectioncreatedtohighlightdatabaselinksthatareofparticularinterestonspecifictargetandligandpages,forexampletheIMGT/mAbDBresourceforantibodies LinksaddedtoneXtProt,aknowledgebaseofhumanproteinsprovidingaccesstoarangeofhighqualitydatasetswithtoolstominethem8 New file formats added to the download page; we now also provide aMySQL version of thedatabase, inadditiontotheoriginalPostgreSQLversion. Ifyouuseeitheroftheseversions,we'daskthatyoupleaseletusknowandwe'dbegratefulforfeedback. AsubstantivecompilationofFAQsisnowavailable Our Helppagesnow include a walkthroughdemoof thewebsiteproducedbyProfessorTonyHarmar prior to his retirement; this resource complements the tutorial already available via ourResourcesmenuandweespeciallyhopeournewuserswillfinditvaluableforgettingtogripswiththesite Ligandsearchtools: Our chemical structure search toolnowuses theMarvin JS structureeditor fromChemAxon,which replaces theolderJavaversion; thenewJavaScriptversionhastheadvantageofcrossplatformcompatibility Thisversionshouldalsobecompatiblewithtabletsandmobiledevices Usefulfeaturesincludetheabilitytoimportmoleculesthroughvariousfileformats,structuralidentifiersorbycompoundname Compoundscanalsobeexportedinmanydifferentformatsorasanimagefile2. Generaloverviewofthecontentofthedatabase: ConcisetargetfamilysummarypagesareavailableforGPCRs,voltage,ligandgated,andotherionchannels,nuclearhormonereceptors,catalyticreceptors,transportersandenzymes,otherproteintargetshasnowbeenadded MoredetailedviewsareavailableforallGPCRs,voltageandligandgatedionchannels,andnuclearhormonereceptors Expandabletreenavigationschemeforallthetargetsintheresource3. Targetupdates: GPCRupdates:Adenosine2A,Angiotensin,Bombesin,Bileacid,Calcitonin,ClassFrizzledGPCRs,Complement C5a1 and C5a2 receptors, Dopamine D1, D3 and D5 receptors, Formylpeptide,Lysophospholipid (LPA) and Lysophospholipid (S1P), Melanocortin, Melaninconcentratinghormone, Melatonin, Neuromedin U, Neuropeptide FF/neuropeptide AF, P2Y1 and P2Y12receptors,Parathyroidhormone,Plateletactivating,Somatostatin sst3and sst5 receptors,TraceamineTA1 LinkstoBitterDBaddedforTaste2Receptors CrosslinksaddedbetweenGPCRDBandGtoPdb,andtheUniProtandHGNCdatabasesnowlinktoGtoPdb DataonexperimentallygeneratedmutationsfromGPCRDB Voltagegatesionchannelupdates:Inwardlyrectifyingpotassiumchannels,K2Pchannels,TwoPpotassiumchannels,Voltagegatedcalciumchannels,Voltagegatedpotassiumchannels,Voltagegatedsodiumchannels Enzymeupdates:curationofphaseIIIkinaseinhibitorsand~20proteaseclinicalcandidatesorleadcompounds,e.g.BACE1 Proteaseupdates:Thistargetclassnowincludesafirst(forthedatabase)withapredrug>prodrug>drugtriplet;thesewerecuratedfromapaperdescribinghowMMP12producesitsowninhibitorina twostep activation procedure; we now have ligand entries for the peptide substrate of theprotease, the prodrug and the drug; Increased ligandmappings to FII (thrombin) ACE, PSEN1,BACE1andBACE2 Kinaseandepigenetictargetupdates:affinitydataformanykinase inhibitors includingthose inclinical trials; several new epigenetics targets added into the Other Protein Targets section,includingchromatinmodifyingenzymes,bromodomaincontainingproteins,ribosomalfactorsandkelchlikeproteins Disease information updates: target pathophysiology updated with standardised diseasenomenclature;diseasesynonyms;addedDiseaseOntologynomenclatureandlinkstotheOntobeediseaseontologybrowser;morelinksaddedtotheOMIMandOrphanetdiseasedatabases4. Ligandupdates:9 HighspecificitycalloutsfromligandpagestoPubMedclinicaltrialreports;N.B.theuseofcalloutsforusersoffersaninstantupdatefromPubMedasopposedtoastaticlink Structuralandclinicalinformationfor>500approveddrugs,takingourtotaldrugcountupto1,201 Eachof the tabsonour ligand list isnowannotatedwithour approveddrug symbol, indicatingapproveddrugligandswithineachclass Annotationof,andcrosslinkingbetweenprodrugsandtheiractiveforms Creatednewcategoryof labelled ligands to includeunstable isotopes, fluorescent tagsor smallchemicalentities Completedaqualitycontrolcheck inconsultationwithPubChemandmanyentriesnowupdatedwithCIDsandcontextualcomments(detailswillbeaddedtoourblog) Addedactivitydata forapproved,clinicalcandidateand researchdrugs for targets inAlzheimer'sdisease NCATSandAstraZenecarepurposingcompoundsadded Newmonoclonalantibodiesandsmallmoleculesincludedinpharmapipelines(includinganynoveldrugtargets) Sourced available binding affinity data for all monoclonal antibodies in the database using acombinationofBLASTsequenceanalysis,patentand literaturesearches,taggingprimarytargetsasappropriate AddedalltheunblindedcompoundsfromSGC'sepigeneticscompoundrepository Ligands modulating epigenetic targets (chromatin modifying enzymes and bromodomaincontainingproteins)fromseveralrecentreviews Manynewkinaseinhibitors5. Linksandinteractionswithotherresources: BindingDBSubsequenttoavisitfromMichaelGilsoninJune(PIforBindingDB)wehaveextendedour interactionsviaTCs. It transpires thisdatabasehasbothunique featuresand target> ligandcontentthatwecanutilize.Theuniquecontentarisesfromtheirparticularscopeof literatureandpatentextractionthatextendstopublicationsneithercoveredbyourselvesnorChEMBL. EBIDatabaseTeamsThroughvisitsandteleconferenceswehaveextendedourvaluablecontactswithgroupson theHinxtonCampus includingUniProt (BenoitBely),Reactome (Steve Jupe)andMEROPS(NeilRawlings).Technicaldiscussionshavecentredonenhancingreciprocalcrosslinking ECNPWeareworkingwithECNPinordertoprovidethemolecularbasisfortheirclassificationofpsychiatrydrugs.WehavenowcuratedallthedrugsinthefullECNPlistalongwithactivitydata.AnewversionoftheECNPappwillincludelinksfromdrugnamestothedatabase GPCRDBWenowhavereciprocallinksbetweenthetwodatabasesandareworkingtoextendtheinteroperabilitybetweenourtworesourcesaswellasapplyingforjointfundingfortheseprojects.In April, Joanna Sharman attended and presented a poster at the Barcelona GPCR SpringConferenceorganisedbytheGLISTENnetwork.ThisincludedpresentinganddiscussingproposalsforcollaborationsattheGPCRDBSatelliteMeeting.JoannarecentlyattendedafivedayworkshoponwebservicesatRadboudUniversityinNijmegen,organisedbyProfGerritVriend.AsmallgroupofdevelopersofGPCRresources(includingGPCRDB)attendedtheworkshopto learnhowtousetheGPCRDBwebservicesandtoexplorethetechnicalitiesofsharingdatabetweenourresources.Further discussions on our collaboration took placewhenAdam Pawson attended theGPCRDBsatelliteworkshopattheGLISTENBudapest2014Conference,24thOctober. OrphanetWehavehadrecentdiscussionswiththeOrphanetteamtoprovideadditionalreciprocallinks between our resources and to increase the visibility of GtoPdb on the Orphanet site. Inaddition,wehavehadrecentdiscussionswithAnaRathoninteractionsbetweenourresourcesforfuturefundingapplications. PubChem Wecontinue to increase thevisibilityandutilityofourcrosslinksanddataentries inPubChem.ThisincludescollaborativeengagementwiththeirteamconcerningQCofourstructuresandarangeofenhancements (seeJunenewsletter fordetails).Consequenttoourrelease2014.2we now have 7652 substance identifiers (SIDs) and 5713 compound identifiers (CIDs) (thesenumbers will change after our next release). Note that every SID links back to us via the10GTPLXXXXlinkandtheseareincludedinthesourcemappingsforeachoftheCIDs.TheexcessofSIDsoverCIDs reflectsourentries thatdonothavechemical structure representations (i.e. theycannot bemerged into CIDs). Themajority of these are peptides but it includes our antibodyentries.Viaaprocessof internalcrosscheckingwehavealsobeenabletoreviseselectedentriesandaddnewones,betweenourmajorrefreshsubmissions.WiththePubChemBioAssayteamweare looking at our interaction data with a view to updating and scalingup our activity resultdepositions.Thiswillofferpowerfulnewqueryoptionsnot just forour customersbut theentirePubChemuserbase. UniversityofEdinburghSchoolof Informatics Thedatabase teamhasa longtimecollaborationwithPeterBunemansDatabaseGroupandarecollaboratorsonhisUSfundedDataCitationgrant.PeterorganisedaworkshopattendedbyJoannaonComputationalChallenges inDataCitationatthe University of Pennsylvania, Philadelphia, which brought together three groups of people(Computer Scientists, Information Scientists and Data Scientists) to explore the technicalchallengesand researchopportunitiesposedby the increasingdemand togenerate citations forlarge, complexdatasets.Oneof theaimsof thedata citationgrant is todevelop computationalsolutionstotheproblemofarchivingandcitingcomplexandchangingdata.ThusJoannaisworkingwithPeterand colleaguesatUPennondevelopingamechanism toarchive theGtoPdb inXML,whichwouldnotonlyallowversionsof ittobecitedbutcouldalsobeconverted intoadocumentformat,whichcouldthenformthebasisofthenextConciseGuideProductionofTheConciseGuidetoPHARMACOLOGY2014/15A major effort for the database team in the coming months is the production of The Concise Guide toPHARMACOLOGY2014/15(thenextbiennialupdatetothe2013/14edition),whichwillbeasnapshotoftheconcisetarget family summaries in the database, published as a series of PDFs, and intended to be a quick desktopreferenceguide.Detailsofthepublicationprocess: TheEditorsoftheConciseGuideareSteveAlexanderandJohnPeters,withEamonnKellyandNeilMarrionjoiningasEditorsin2015 The2014/15editionoftheConciseGuidewillbepublishedinautumn2015 Over170expertcollaboratorscontributedtoupdatingtheconcisetargetfamilysummariesinthedatabaseinpreparationforpublication We are developing a method of producing the content from an XML version of the database, incollaborationwithcolleaguesintheSchoolofInformatics ThePDFfileswillbeinlandscapeformat,andincludeembeddedhyperlinksfromgenenamesandUniProtIDs direct to HGNC and UniProt entries respectively, from target and ligand names direct to theIUPHAR/BPSGuidetoPHARMACOLOGY,andfromPubMedIDsdirecttoPubMedcitationsAcknowledgementsWeareverygratefultooursponsors.Wearealso immenselygratefulfortheworkdonebyourcolleagues inNCIUPHARandallthecontributingchairsandsubcommitteemembers.Itisaprivilegetobeassociatedwithsomuchwork freelygiven for thegoodof science.We repeat thatNCIUPHAR isaglobal resourceandall scientistsarewelcometocontribute(contact:curators@guidetopharmacology.org;enquiries@guidetopharmacology.org).11AppendixI:MembershipofNCIUPHARChair(outgoing)MichaelSpedding,FranceViceChairsAnthonyDavenport,UKChairmanEvolvingPharmacologyAnthonyHarmar,UKDatabaseChairmanRickNeubig,USAGPCRsEliotOhlstein,USAEditorMembersStephenAlexander,UKThomasBonner,USAWilliamCatterall,USAArthurChristopoulos,AustraliaJohnCidlowski,USASirColinT.Dollery,UKDorianoFabbro,SwitzerlandKozoKaibuchi,Japan*YoshikatsuKanai,Japan*JohnPeters,UKAlexPhipps,UKJeanPhilippePin,FranceExOfficioSamEnna,USAIUPHARPresidentMichaelSpedding,FranceIUPHARSecretaryGeneralPetraThrmann,GermanyIUPHARTreasurerSimonMaxwell,UKEducationalSiteProjectLeaderJamieDavies,UKDatabasePrincipalInvestigatorJoannaSharman,UKDatabaseDeveloperAdamPawson,UKSeniorDatabaseCuratorHelenBenson,UKDatabaseCuratorElenaFaccenda,UKDatabaseCuratorChristopherSouthan,SwedenChemicalCuratorVeronikaDivincova,UKProjectAdministratorElspethBruford,UKrepresentingHGNCPastChairs(ExOfficio)PaulVanhoutte,HongKongBobRuffolo,USACorrespondingMembersSusanAmara,USAMichelBouvier,CanadaThomasBurris,USAStephenCharlton,UKMosesChao,USAStevenL.Colletti,USAGrahamCollingridge,UKSueDuckles,USARichardEglen,UKStevenFoord,UKDavidGloriam,DenmarkGillianGray,UKDebbieHay,NewZealandAllynHowlett,USAFranzHofmann,GermanyYuHuang,HongKongAdP.Ijzerman,TheNetherlandsMichaelF.Jarvis,USABongKiunKaang,KoreaTerryKenakin,USAJanosKiss,HungaryStefanKnapp,UKChrisLangmead,AustraliaVincentLaudet,FranceMargaret(Mandy)MacLean,UKFionaMarshall,UKAlistairMathie,UKIanMcGrath,UKGraemeMilligan,UKStefanOffermanns,GermanyRichardOlsen,USAHelgiSchith,SwedenGraemeSemple,USADavidSearls,USARolandStaal,USABartStaels,FranceGeorgTerstappen,GermanyMaryVore,USAClinicalTranslationalPharmacologyGroup(corememberSirColinDollery)EdBullmore,UKRobertDow,UKGarrettFitzgerald,USAAlexPhipps,UKPatrickduSouich,CanadaDavidWebb,UKDonBirkett,Australia12AppendixII:NCIUPHARSubcommittees(listingofchairs)GproteincoupledreceptorsSubcommittees5Hydroxytryptamine:NickBarnes,JohnNeumaierAcetylcholine(muscarinic):ArthurChristopoulos Adenosine:AdriaanIzjermanalpha1adrenoceptors:DiannePerez alpha2adrenoceptors:MikaScheinin Angiotensin:SadashivaKarnikApelin:AnthonyDavenport betaadrenoceptors:TerryHbert Bileacid:AnthonyDavenportBombesin:RobertJensen Bradykinin:VACANT Calcitonin:DebbieHay,DavidPoynerCalciumsensing:EdBrown,HansBrunerOsborneCannabinoid:RogerPertwee,AllynHowlett Chemokine:PhilipMurphyCholecystokinin:LaurenceMiller Complementpeptide:PeterMonkCorticotropinreleasingfactor:RichardHauger,FrankDautzenbergDopamine:RaulGainetdinov Endothelin:AnthonyDavenport Estrogen(Gproteincoupled):VACANTFormylpeptidefamily:RichardYe Freefattyacid:VACANT Frizzled:GunnarSchulteGABAB:BernhardBettler Galanin:AndrewGundlach Ghrelin:BirgitteHolstGlucagonreceptorfamily:LaurenceMiller Glycoproteinhormone:DeborahSegaloffGonadotrophinreleasinghormone:AdriaanIjzermanHistamine:PaulChazot Hydroxycarboxylicacid:StefanOffermanns Kisspeptin:AnthonyDavenportLeukotriene:MagnusBck Lysophospholipid(LPA):JeroldChung Lysophospholipid(S1P):SarahSpiegelMelaninconcentratinghormone:JeanLouisNahonMelanocortin:TungFong,HelgiSchith Melatonin:RalfJockersMetabotropicglutamate:JeanPhilippePin Motilin:AnthonyDavenport NeuromedinU:GaryWillarsNeuropeptideFF/neuropeptideAF:JeanMarieZajacNeuropeptideS:GirolamoCalNeuropeptideW/neuropeptideB:AnthonyDavenportNeuropeptideY:DanLarhammar Neurotensin:JeanMazella Opioid:LarryTollOrexin:ChristopherWinrow P2Y:GeoffreyBurnstock Parathyroidhormone:JeanPierreVilardagaPeptideP518:JeromeLeprince Plateletactivatingfactor:VACANT Prokineticin:PhilippeRondardProlactinreleasingpeptide:HelgiSchith Prostanoid:XavierNorel Proteaseactivated:NigelBunnettRelaxinfamilypeptide:RogerSummers Relaxinlike:NickBarker Somatostatin:StephanSchulzTachykinin:SusanLeeman,StevenDouglas Traceamine:JanetMaguireThyrotropinreleasinghormone:MarvinGershengornUrotensin:HubertVaudry Vasopressinandoxytocin:BernardMouillac VIPandPACAP:JosephPisegnaLigandgatedionchannelsSubcommitteesJohnPeters(LiaisonforallLGICsubcommittees)VoltagegatedionchannelsSubcommitteesWilliamCatterall(LiaisonforallVGICsubcommittees)NuclearhormonereceptorsSubcommitteesJohnCidlowskiandThomasBurris(LiaisonsforallNHRsubcommittees5HT3:JohnPetersGABAA:RichardOlsenGlycine:JosephLynchIonotropicglutamate:GrahamCollingridgeNicotinicacetylcholine:NeilMillarP2X:CharlesKennedyZAC:TimothyHalesAdenylylcyclasesSubcommitteeCarmenDessauerAntibodiesSubcommitteeAlexPhippsDrugTargetandChemistryCurationSubcommitteeChristopherSouthanEpigeneticsSubcommitteeRabinderPrinjhaCalciumactivatedpotassium:LenKaczmarekCatSperandTwoPore:DavidChapmanCyclicnucleotideregulated:MartinBielInwardlyrectifyingpotassium:PaulSlesingerTransientReceptorPotential:DavidClaphamTwoPpotassium:StevenGoldsteinVoltagegatedcalcium:WilliamCatterallVoltagegatedpotassium:LilyJanVoltagegatedsodium:WilliamCatterallGasotransmittersSubcommitteeAndreasPapapetropoulos,CsabaSzaboGuanylylcyclasesSubcommitteeAdrianHobbs,ScottWaldmanKinasesSubcommitteeDorianoFabbroNoncodingRNAsSubcommitteeAndrewBakerAndrogenreceptors:NancyWeigelProgesteroneReceptors:DeanEdwardsEstrogenreceptors:KennethKorachThyroidhormonereceptors:DouglasForrestVitaminDreceptors:J.WesleyPikeMineralocorticoidreceptors:PeterFullerLXRreceptors:DonaldMcDonnellGlucocorticoidreceptors:RobertOakley,DerekCainRORreceptors:AntonJettenPatternRecognitionReceptorsSubcommitteeClareBryantProteasesSubcommitteeAnthonyTurnerTransportersSubcommitteeStephenAlexanderConciseGuidetoPHARMACOLOGYEditorsStephenAlexander,JohnPeters,EamonnKelly,NeilMarrion13AppendixIII:NCIUPHARbadgedpublicationsNCIUPHARpublicationsinPharmacologicalReviews(2014/15)BryantCE,OrrS,FergusonB,SymmonsMF,BoyleJP,andMonieTP.(2015)InternationalUnionofBasicandClinicalPharmacology.XCVI.PatternRecognitionReceptorsinHealthandDisease.PharmacolRevApril201567:462504HallsML,BathgateRA,SuttonSW,DschietzigTB,SummersRJ.(2015)InternationalUnionofBasicandClinicalPharmacology.XCV.Recentadvancesintheunderstandingofthepharmacologyandbiologicalrolesofrelaxinfamilypeptidereceptors14,thereceptorsforrelaxinfamilypeptides.PharmacolRev.67:389440.[PMID:25761609]HamannJ,AustG,AraD,EngelFB,FormstoneC,FredrikssonR,HallRA,HartyBL,KirchhoffC,KnappB,KrishnanA,LiebscherI,LinHH,MartinelliDC,MonkKR,PeetersMC,PiaoX,PrmelS,SchnebergT,SchwartzTW,SingerK,StaceyM,UshkaryovYA,VallonM,WolfrumU,WrightMW,XuL,LangenhanT,SchithHB.(2015)InternationalUnionofBasicandClinicalPharmacology.XCIV.AdhesionGProteinCoupledReceptors.PharmacolRev.67:33867.[PMID:25713288]GardellaTJ,VilardagaJP.(2015)InternationalUnionofBasicandClinicalPharmacology.XCIII.TheParathyroidHormoneReceptorsFamilyBGProteinCoupledReceptors.PharmacolRev.67:31037.[PMID:25713287]VaudryH,LeprinceJ,ChatenetD,FournierA,LambertDG,LeMvelJC,OhlsteinEH,SchwertaniA,TostivintH,VaudryD.(2015)InternationalUnionofBasicandClinicalPharmacology.XCII.UrotensinII,urotensinIIrelatedpeptide,andtheirreceptor:fromstructuretofunction.PharmacolRev.67:21458.[PMID:25535277]KellenbergerS,SchildL.(2015)InternationalUnionofBasicandClinicalPharmacology.XCI.Structure,Function,andPharmacologyofAcidSensingIonChannelsandtheEpithelialNa+Channel.PharmacolRev.67:135.[PMID:25287517]ChristopoulosA,ChangeuxJP,CatterallWA,FabbroD,BurrisTP,CidlowskiJA,OlsenRW,PetersJA,NeubigRR,PinJP,SextonPM,KenakinTP,EhlertFJ,SpeddingM,LangmeadCJ.(2014)InternationalUnionofBasicandClinicalPharmacology.XC.MultisitePharmacology:RecommendationsfortheNomenclatureofReceptorAllosterismandAllostericLigands.PharmacolRev.66:918947.[PMID:25026896]BachelerieF,BenBaruchA,BurkhardtAM,CombadiereC,FarberJM,GrahamGJ,HorukR,SparreUlrichAH,LocatiM,LusterAD,MantovaniA,MatsushimaK,MurphyPM,NibbsR,NomiyamaH,PowerCA,ProudfootAE,RosenkildeMM,RotA,SozzaniS,ThelenM,YoshieO,ZlotnikA.(2014)InternationalUnionofBasicandClinicalPharmacology.LXXXIX.UpdateontheExtendedFamilyofChemokineReceptorsandIntroducingaNewNomenclatureforAtypicalChemokineReceptors.PharmacolRev.66:179.[PMID:24218476]NCIUPHARreviewsintheBritishJournalofPharmacology(2014/15)FabbroD,CowanJacobSW,MoebitzH.(2015)"10thingsyoushouldknowaboutproteinkinases"IUPHARReview14BrJPharmacol.2015Jan29.DOI:10.1111/bph.13096[Epubaheadofprint][PMID:25630872]BeaulieuJM,EspinozaS,GainetdinovRR.(2014)Dopaminereceptors:anupdateIUPHARReview13BrJPharmacol.172:123.[PMID:25671228]MaguireJJ,DavenportAP.(2014)Endothelin@25newagonists,antagonists,inhibitorsandemergingresearchfrontiers:IUPHARReview12BrJPharmacol.171:555572.[PMID:25131455]ToughDF,LewisHD,RiojaI,LindonMJ,PrinjhaRK.(2014)Epigeneticpathwaytargetsforthetreatmentofdisease:acceleratingprogressinthedevelopmentofpharmacologicaltools:IUPHARReview11.BrJPharmacol.171:49815010.[PMID:25060293]FujitaW,GomesI,DeviLA.(2014)RevolutioninGPCRSignaling:Opioidreceptorheteromersasnoveltherapeutictargets:IUPHARReview10.BrJPharmacol.171:415576.[PMID:24916280]CoxBM,ChristieMJ,DeviL,TollL,TraynorJR.(2014)Challengesforopioidreceptornomenclature:IUPHARReview9.BrJPharmacol.172:31723[PMID:24528283]KiharaY,MaceykaM,SpiegelS,ChunJ.(2014)Lysophospholipidreceptornomenclaturereview:IUPHARReview8.BrJPharmacol.171:357594.[PMID:24602016]BckM,PowellWS,DahlnSE,DrazenJM,EvansJF,SerhanCN,ShimizuT,YokomizoT,RovatiGE.(2014)InternationalUnionofBasicandClinicalPharmacology.UpdateonLeukotriene,LipoxinandOxoeicosanoidReceptors:IUPHARReview7.BrJPharmacol.171:355174.[PMID:24588652]DolleryCT.(2014)LostinTranslation(LiT):IUPHARReview6.BrJPharmacol.171:226990.[PMID:24428732]14SchulzS,LehmannA,KliewerA,NagelF.(2014)Finetuningsomatostatinreceptorsignallingbyagonistselectivephosphorylationanddephosphorylation:IUPHARReview5.BrJPharmacol.171:15919.[PMID:24328848]BonnerTI.(2014)Shouldpharmacologistscareaboutalternativesplicing?IUPHARReview4.BrJPharmacol.171:123140.[PMID:24670145]DijksterhuisJP,PetersenJ,SchulteG.(2014)WNT/Frizzledsignalling:receptorligandselectivitywithfocusonFZDGproteinsignallinganditsphysiologicalrelevance:IUPHARReview3.BrJPharmacol.171:11951209.[PMID:24032637]AdditionalGtoPdbCurationTeampublicationsthatincludetheWellcomeTrustgrantacknowledgmentSouthanC.(2015)Expandingopportunitiesforminingbioactivechemistryfrompatents.DrugDiscoveryToday:Technologies.2015Feb10.doi:10.1016/j.ddtec.2014.12.001[Epubaheadofprint]LipinskiCA,LittermanNK,SouthanC,WilliamsAJ,ClarkAM,EkinsS.(2014)ParallelWorldsofPublicandCommercialBioactiveChemistryData.JMedChem.2014Dec4.[Epubaheadofprint][PMID:25415348]15AppendixIV:DatabaseStatisticsTargetclass Numberoftargets7TMreceptors 395Gproteincoupledreceptorsincludingorphans 389OrphanGproteincoupledreceptors 129Other7TMproteins 6Nuclearhormonereceptors 48Catalyticreceptors 239Ligandgatedionchannels 84Voltagegatedionchannels 141Otherionchannels 47Enzymes 1148Transporters 508Otherproteintargets 116Totalnumberoftargets 2726 Chemicalclass NumberofligandsSyntheticorganics 4734Metabolites 582Endogenouspeptides 732Otherpeptidesincludingsyntheticpeptides 1181Naturalproducts 220Antibodies 103Inorganics 34Approveddrugs 1201Withdrawndrugs 63DrugswithINNs 1768Labelledligands 580Totalnumberofligands 7586 Numberofcuratedbindingconstants 12829Numberofbindingconstantsfromlargescalescreens 31207Numberofreferences 2600116AppendixV:Fundsavailableasof31stMarch2015**IUPHARandBPScontributions: 58,025.33(forsalariesonly)WellcomeTrustgrant: 134,703.00(forsalaries,meetings,travel,etc.)Totalfundsavailable: 192,728.33**ThesefiguresdonotincludecontributionsfromotherNCIUPHARincomesourcesThisreportwascompiledbyAdamPawsonandMichaelSpedding,March,2015

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