Tolvaptan-OPC-41061-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemETolvaptanCat.No.:HY-17000CASNo.:150683-30-0Synonyms:OPC-41061分?式:C??H??ClN?O?分?量:448.94作?靶點:VasopressinReceptor;Autophagy作?通路:GPCR/GProtein;Autophagy儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:≥100mg/mL(222.75mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.2275mL11.1373mL22.2747mL5mM0.4455mL2.2275mL4.4549mL10mM0.2227mL1.1137mL2.2275mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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)1/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.17mg/mL(4.83mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.17mg/mL(4.83mM);ClearsolutionBIOLOGICALACTIVITY?物活性Tolvaptan?種選擇性，競爭性并且具有?服活性的vasopressinreceptor2(V2R)拮抗劑，抑制AVP誘導(dǎo)的??板聚集，其IC50值為1.28μM。Tolvaptan可誘導(dǎo)細胞凋亡，響細胞周期。Tolvaptan可?于低鈉?癥的研究。體外研究Tolvaptan(0-100μM;24-168h)decreasesthegrowthofHepG2cells[2].Tolvaptan(20-100μM;24-48h)inducescelldeathinHepG2cells[2].Tolvaptan(0-100μM;24-48h)affectscellcycleofHepG2cells[2].Tolvaptan(0-100μM;24-48h)causesDNAdamageandinducesapoptosisofHepG2cells[2].Tolvaptan(0-100μM;24-48h)decreasescyclinsandCDKs,andincreasesγ-H2AX,PARPcleavageandLC3B-IIinHepG2cells[2].Tolvaptan(0-100μM;4-24h)inducesphosphorylationofJNK,ERK1/2andp38inHepG2cells[2].Tolvaptan(0-100μM;24-28h)inducesautophagyofHepG2cells[2].CellViabilityAssay[2]CellLine:HepG2cellsConcentration:0-100μMIncubationTime:24,48,96and168hoursResult:Time-anddose-dependentlyinhibitedHepG2cellswithIC50sof＞100,52.2,33.0and27.1μMat24,48,96and168hours,respectively.CellViabilityAssay[2]CellLine:HepG2cellsConcentration:20,40,60,80,and100μMIncubationTime:24and48hoursResult:Time-anddose-dependentlyinhibitedHepG2cellgrowthandcausedcelldeath,withLDHreleasedataconcentrationover40μM.CausedoxidativeDNAdamageandincreasedROSproductionwithaconcentrationof60-100μM.CellCycleAnalysis[2]CellLine:HepG2cellsConcentration:0-100μM2/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEIncubationTime:24and48hoursResult:CausedcellcyclearrestattheG2phase,dose-dependentlyincreasedthepercentageofG0/G1phasecellswithaconcentrationof20-60μMandincreasedthepercentageofG2/Mphasecellswithaconcentrationof60-100μM.WesternBlotAnalysis[2]CellLine:HepG2cellsConcentration:0-100μMIncubationTime:24and48hoursResult:Dose-dependentlydecreasedcyclinD1,cyclinD3,cyclinB1,CDK1,CDK2,CDK4,andCDK6,andincreasedγ-H2AXwhichisamakerofDNAdoublestrandbreaksinHepG2cells.IncreasedthefulllengthPARPintocleavagesituationandinducedPARPcleavage.ApoptosisAnalysis[2]CellLine:HepG2cellsConcentration:0-100μMIncubationTime:24and48hoursResult:Inducedcellapoptosiswithincreasingcaspase3/7activityatadoseover40μM.WesternBlotAnalysis[2]CellLine:HepG2cellsConcentration:0-100μMIncubationTime:4and24hoursResult:InducedtheactivationofERK1/2andp38after4or24hofexposureataconcentrationover60μMinHepG2cells.CellAutophagyAssay[2]CellLine:HepG2cellsConcentration:0-100μMIncubationTime:24and48hoursResult:Inducedcellautophagywithautophagosomeformationandanincreasinglysosomal3/4MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEturnoverrate.體內(nèi)研究Tolvaptan(10mg/kg;p.o.onceperdayfor22days)improvescyclophosphamide(CP)-inducednephrotoxicityinrats[3].AnimalModel:Malealbinoratswithcyclophosphamideintraperitonealinjection[3]Dosage:10mg/kgAdministration:Oralgavage;10mg/kgonceperday;for22daysResult:Improvedthelevelofurinevolume,serumNa+,serumosmolarity,urinarycreatinine,freewaterclearance,serumcreatinine,urea,serumK+,bloodpressure,urineosmolarity,fractionalexcretionofsodiumandsignsofnephrotoxicityinmice.Decreasedcaspase-3,Baxandpro-inflammatorycytokines,andincreasedantiapoptoticBcl-2inrenaltissueofmice.戶使?本產(chǎn)品發(fā)表的科研?獻?JAmSocNephrol.2018Nov;29(11):2658-2670.?JMedChem.2022May17.?IntJMolSci.2019Nov16;20(22):5764.?FASEBJ.2019Jan;33(1):469-483.?EurJPharmacol.2020Aug5;880:173157.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WuY,etal.Mechanismsoftolvaptan-inducedtoxicityinHepG2cells.BiochemPharmacol.2015Jun15;95(4):324-36.[2].El-ShabrawyM,etal.Protectiveeffectoftolvaptanagainstcyclophosphamide-inducednephrotoxicityinratmodels.