Velusetrag-TD-5108-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVelusetragCat.No.:HY-10457CASNo.:866933-46-2Synonyms:TD-5108分?式:C??H??N?O?S分?量:504.64作?靶點(diǎn):5-HTReceptor作?通路:GPCR/GProtein;NeuronalSignaling儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:100mg/mL(198.16mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9816mL9.9081mL19.8161mL5mM0.3963mL1.9816mL3.9632mL10mM0.1982mL0.9908mL1.9816mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：(為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥5.48mg/mL(10.86mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥5.75mg/mL(11.39mM);ClearsolutionBIOLOGICALACTIVITY?物活性Velusetrag(TD-5108)?種具有?服活性，有效和選擇性的?素5-HT4受體(5-HT4R)激動(dòng)劑，pKi為7.7。Velusetrag對(duì)5-HT2A和5-HT2B受體沒有親和?(Ki>10μM)。Velusetrag可?于胃腸道疾病和帕?森病的研究[1][2][3][4][5]。IC50&Target5-HT4Receptor7.7(pKi)體外研究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].體內(nèi)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?邊的抑制劑?師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: