VU0530244

[3] Serotonin 5-HT2B receptor antagonists are of interest for potential use in medicine to treat pulmonary arterial hypertension, valvular heart disease, and related cardiopathies.[4][5][6][3] However, reduced serotonin 5-HT2B receptor signaling in the central nervous system has been linked to adverse effects such as impulsivity, suicidality, and sleep disturbances, among others.[8][9][10][11][12] Serotonergic psychedelics like lysergic acid diethylamide (LSD) and psilocybin as well as entactogens like MDMA are also potent serotonin 5-HT2B receptor agonists, and there have been concerns about chronic administration of these and related agents in medical contexts due to possible development of cardiac and other complications.[13][14][15][16] Selective serotonin 5-HT2B receptor antagonism has been found to fully prevent the cardiotoxicity of dexnorfenfluramine in rodents.[17][18] In 2024, the paper that described the discovery of the VU0530244 won the 2023 Rosalind Franklin Society Special Award in Science for contributions to the journal Assay and Drug Development Technologies.
Drug classSelectiveperipherally restrictedserotonin5-HT2B receptorantagonistIUPAC nameCAS NumberChemSpiderFormulaMolar massSMILESpotenthigh-throughput screeningaffinity5-HT2A5-HT2C receptorsP-glycoproteinsubstrateblood–brain barrierpermeabilitymedicinepulmonary arterial hypertensionvalvular heart diseasecardiopathiessignalingcentral nervous systemadverse effectsimpulsivitysuicidalitysleep disturbancescardiac fibrosisvalvulopathypulmonary hypertensionserotonergic agentscabergolineergotaminemethysergidepergolideserotonin releasing agentschlorphentermineaminorexfenfluraminedexfenfluraminebenfluorexSerotonergic psychedelicslysergic acid diethylamidepsilocybinentactogenscardiotoxicitydexnorfenfluramineBW-501C67XylamidineSerotonin receptormodulators5-HT1A8-OH-DPATAdatanserinAmphetamineAntidepressantsetoperidonehydroxynefazodonenefazodonetrazodonetriazoledionevilazodonevortioxetineAtypical antipsychoticsaripiprazoleasenapinebrexpiprazolecariprazineclozapinelurasidonequetiapineziprasidoneAzapironesbuspironeeptapironegepironeperospironetandospironeBay R 1531BefiradolBMY-14802CannabidiolDimemebfeDopamineEbalzotanEltoprazineEnciprazineErgolinesbromocriptinedihydroergotaminelisuridemethylergometrine (methylergonovine)F-11,461F-15063F-15,599FlesinoxanFlibanserinFlumexadolHypidoneLesopitronLY-293284MKC-242NaluzotanOsemozotanOxaflozanePardoprunoxPiclozotanRauwolscineRepinotanRoxindoleRU-24,969S-14,506S-14671S-15535SarizotanSerotonin (5-HT)SunepitronTryptamines5-MeO-DMTbufoteninindorenateN-Me-5-HTpsilocinTGBA01ADU-92,016-AUrapidilXaliprodenYohimbineiloperidonerisperidonesertindoleBeta blockersalprenololcarteololcyanopindololiodocyanopindololisamoltaneoxprenololpenbutololpindobindpindololpropranololtertatololBMY-7,378CSP-2503DotarizinemetergolineFlopropioneLecozotanMefwayMetitepine (methiothepin)MIN-117 (WF-516)NAN-190RobalzotanSB-649,915SpiperoneSpiramideSpiroxatrineUH-301WAY-100135WAY-100635AcetryptineCarvedilolergometrine (ergonovine)5-HT1BAnpirtolineCGS-12066ACP-93129CP-94253CP-122,288CP-135807TriptansavitriptandonitriptaneletriptansumatriptanzolmitriptanAR-A000002ElzasonanGR-127935LY-393558SB-216641SB-2360575-HT1DL-694247PNU-142633almotriptanfrovatriptannaratriptanrizatriptan5-Et-DMT5-(nonyloxy)tryptamineAlniditanBRL-15,572KetanserinLY-310762LY-367642LY-456219LY-456220MianserinRitanserinlysergol5-HT1EBRL-54443tryptamine5-HT1FLasmiditanLY-33437025I-NBF25I-NBMD25I-NBOH25I-NBOMe25B-NBOMe25C-NBOMe25TFM-NBOMe2CBCB-NBOMe25CN-NBOH2CBFly-NBOMe2C-T-22C-T-72C-T-212C-B-FLY2CB-Ind5-Methoxytryptamines5-MeO-DET5-MeO-DiPT5-MeO-DPTα-Alkyltryptamines5-Cl-αMT5-Fl-αMT5-MeO-αET5-MeO-αMTα-Me-5-HTAL-34662AL-37350ABromo-DragonFLYDMBMPPEfavirenz1P-LSDALD-52ergine (LSA)LA-SS-AzLSD-PipIHCH-7113JimscalineLorcaserinMDA (tenamfetamine)MDMA (midomafetamine)O-4310PHA-57378PNU-22394PNU-181731SCHEMBL5334361PhenethylamineslophophinemescalinePiperazinesquipazineTFMFly5-I-R911505-MeO-NBpBrTAC-90179AltanserinAntihistaminescyproheptadinehydroxyzineketotifenperlapineamperozideblonanserincarpipramineclocapramineclorotepinefluperlapinegevotrolinemelperonemosapramineocaperidoneolanzapinepaliperidonezicronapinezotepineChlorprothixeneCinanserinDeramciclaneEplivanserinamesergideLY-215,840mesulerginesergolexoleFananserinGlemanserinKML-010MedifoxamineNaftidrofurylNantenineNelotanserinOpiranserin (VVZ-149)PelanserinPhenoxybenzaminePimavanserinPirenperonePizotifenPruvanserinRoluperidoneSarpogrelateSerotonin antagonists and reuptake inhibitorslubazodonemepiprazoleTeniloxazineTetracyclic antidepressantsamoxapineaptazapineesmirtazapinemaprotilinemirtazapineTricyclic antidepressantsamitriptylineTypical antipsychoticschlorpromazinefluphenazinehaloperidolloxapineperphenazinepimozidepipamperoneprochlorperazinesetoperonethioridazinethiothixenetrifluoperazineVolinanserinnicergoline5-HT2B4-MethylaminorexAmphetaminescloforexlevofenfluraminenorfenfluramineBW-723C86dihydroergocryptineRo60-0175AgomelatineamisulprideN-desmethylclozapine (norclozapine)EGIS-7625LY-272015MetadoxinePRX-08066RS-127445SB-200646SB-204741SB-206553SB-215505SB-221284SB-228357SDZ SER-082TegaserodTIK-3015-HT2CA-372159AL-38022AAlstonineCP-809101MK-212ORG-12962ORG-37684Ro60-0213VabicaserinWAY-629WAY-161503YM-348CaptodiameDesmetramadolFluoxetineLatrepirdine (dimebolin)RS-102221SB-242084SB-243213TedatioxetineTramadolnortriptylineAlcoholsbutanolethanol (alcohol)trichloroethanolm-CPBGPhenylbiguanideRS-56812SR-572272-Me-5-HTbufotenidine (5-HTQ)Volatiles/gaseshalothaneisofluranetoluenetrichloroethaneYM-31636AlosetronAS-8112AzasetronBatanoprideBemesetron (MDL-72222)BupropionCilansetronDazoprideDolasetronGalanolactoneGranisetronHydroxybupropionLerisetronMemantineOndansetronPalonosetronRamosetronRenzaprideRicasetronThujoneTropanserinTropisetronnitrous oxidesevofluraneZacoprideZatosetronnaphthylpiperazineCapeserodCinitaprideCisaprideCJ-033466MetoclopramideMosapridePrucalopridePRX-03140RS-67,333VelusetragGR-113808L-LysinePiboserodSB-2040705-HT5A2-Br-LSD (BOL-148)Valerenic acidSB-699551E-6801E-6837EMD-386088ST-1936WAY-181187WAY-208466tiospironeAVN-101AVN-211AVN-322AVN-397CerlapirdineEGIS-12,233IdalopirdineMasupirdineMS-245PRX-07034Ro 04-6790SB-258585SB-271046SB-357134SB-399885SB-742457clomipraminedoxepinlergotrileBifeprunoxE-55888LP-211ButaclamolDR-4485JNJ-18038683SB-258719SB-269970imipramineacetophenazine