Velusetrag-TD-5108-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEVelusetragCat.No.:HY-10457CASNo.:866933-46-2Synonyms:TD-5108分⼦式:C₂₅H₃₆N₄O₅S分⼦量:504.64作⽤靶点:5-HTReceptor作⽤通路:GPCR/GProtein;NeuronalSignaling储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(198.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9816mL9.9081mL19.8161mL5mM0.3963mL1.9816mL3.9632mL10mM0.1982mL0.9908mL1.9816mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥5.48mg/mL(10.86mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥5.75mg/mL(11.39mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Velusetrag(TD-5108)⼀种具有⼝服活性，有效和选择性的⾎素5-HT4受体(5-HT4R)激动剂，pKi为7.7。Velusetrag对5-HT2A和5-HT2B受体没有亲和⼒(Ki>10μM)。Velusetrag可⽤于胃肠道疾病和帕⾦森病的研究[1][2][3][4][5]。IC50&Target5-HT4Receptor7.7(pKi)体外研究Velusetrag(10pM-100μM)concentration-dependentlyincreasesthecAMPinHEK-293cellsstablytransfectedwiththeh5-HT4(c)receptor,withapEC50of8.3[1].Velusetrag(100pM-1μM)producesconcentration-dependentcontractionoftheguineapigcoloniclongitudinalmuscle/myentericplexus(LMMP),withapEC50of7.9[1].Velusetrag(0.001-10μM)producesaconcentration-dependentrelaxationofthecarbachol(3μM)-precontractedratesophagus,withapEC50of7.9[1].体内研究Velusetrag(3mg/kg;asinglei.p.)significantlyimprovesthefacilitationofcontextualfearextinctioninPDmice[3].Velusetrag(3mg/kg;asinglei.p.)increaseshippocampalcAMPlevelsin1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treatedmice[3].Velusetrag(0.003-3mg/kg;asingles.c.)increasescolonictransitinadose-dependentmannerandreducesthetimetakenforexcretionofthedyeinguineapigs[2].Velusetrag(0.003-1mg/kg;asinglei.v.)dose-dependentlyincreasesinter-crystaldistance,consistentwithrelaxationoftheoesophagusinrats[2].AnimalModel:MaleC57BL/6mice(7-8weeksold)wereinjectedwithMPTP[3]Dosage:3mg/kgAdministration:Asinglei.p.Result:Improvedfacilitationofcontextualfearextinction.DidnotimprovetheimpairedrotarodperformanceinPDmice.REFERENCES[1].SmithJAM,et,al.TheinvitropharmacologicalprofileofTD-5108,aselective5-HT(4)receptoragonistwithhighintrinsicactivity.NaunynSchmiedebergsArchPharmacol.2008Jul;378(1):125-37.[2].BeattieDT,et,al.TheinvivogastrointestinalactivityofTD-5108,aselective5-HT(4)receptoragonistwithhighintrinsicactivity.Naunyn2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESchmiedebergsArchPharmacol.2008Jul;378(1):139-47.[3].IshiiT,et,al.Serotonin5-HT4ReceptorAgonistsImproveFacilitationofContextualFearExtinctioninanMPTP-InducedMouseModelofParkinson'sDisease.IntJMolSci.2019Oct26;20(21):5340.[4].KuoB,etal.Velusetragacceleratesgastricemptyinginsubjectswithgastroparesis:amulticentre,double-blind,randomised,placebo-controlled,phase2study.AlimentPharmacolTher.2021;53(10):1090-1097.[5].GoldbergM,etal.Clinicaltrial:theefficacyandtolerabilityofvelusetrag,aselective5-HT4agonistwithhighintrinsicactivity,inchronicidiopathicconstipation-a4-week,randomized,double-blind,placebo-controlled,dose-responsestudy.AlimentPharmacolTher.2010;32(9):1102-1112.McePdfHeightCaution: