Cyclopamine-11-Deoxojervine-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECyclopamineCat.No.:HY-17024CASNo.:4449-51-8Synonyms:11-Deoxojervine分⼦式:C₂₇H₄₁NO₂分⼦量:411.62作⽤靶点:Hedgehog;Smo;EndogenousMetabolite作⽤通路:StemCell/Wnt;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验Ethanol:20mg/mL(48.59mM;Needultrasonic)DMSO:10mg/mL(24.29mM;ultrasonicandwarmingandheatto80°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4294mL12.1471mL24.2943mL5mM0.4859mL2.4294mL4.8589mL10mM0.2429mL1.2147mL2.4294mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥0.5mg/mL(1.21mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥0.5mg/mL(1.21mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥1mg/mL(2.43mM);Clearsolution4.请依序添加每种溶剂：10%EtOH>>90%cornoilSolubility:≥1.67mg/mL(4.06mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CyclopamineHedgehog通路的拮抗剂，在细胞实验中的IC50为46nM。Cyclopamine还⼀种选择性的Smo抑制剂。IC50&TargetHumanEndogenousMetabolite体外研究TreatmentwithsmallmoleculeHhinhibitorssuchasHhAntagandthenaturalproductCyclopamine,bothbindingtoSmo,inducestumorremissioninageneticmousemodelofmedulloblastoma[1].CyclopamineisaHedgehog(Hh)pathwayantagonist.Cyclopaminesuppressescellgrowth.Cyclopamine(3μM)suppressionofHhpathwayactivityandgrowthindigestivetracttumourcelllinescorrelateswithexpressionofPTCHmRNA[2].CyclopamineisasteroidalalkaloidthatinhibitsHhsignallingthroughdirectinteractionwithSmo[3].体内研究Cyclopaminecausesdurableregressionofxenografttumors.TumorsinCyclopamine-treatedanimals,regresscompletelyby12days[2].Cyclopamine(1.2mg)treatmentblockstumourformationofhumanpancreaticadenocarcinomacellsaftertransplantationintonudemice[3].PROTOCOLCellAssay[2]Cellsareculturedintriplicatein96-wellplatesinassaymediatowhich5E1monoclonalantibody,ShhNpand/orCyclopamine(3μM)areaddedat0hatconcentrationsindicatedinthemaintext.Viablecellmassisdeterminedbyopticaldensitymeasurementsat490nm(OD490)at2and4daysusingtheCellTiter96colorimetricassay.RelativegrowthiscalculatedasOD(day4)-OD(day2)/OD(day2)[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]Atotalof0.1mLHanks’balancedsaltsolutionandmatrigel(1:1)containing2×106cellsisinjectedsubcutaneouslyintoCD-1nudemice.Tumorsaregrownfor4daystoaminimumvolumeof125mm3;treatmentisinitiatedsimultaneouslyforallsubjects.Miceareinjectedsubcutaneouslywithvectoralone(triolein:ethanol4:1v/v)oraCyclopaminesuspension(1.2mgpermouseintriolein:ethanol4:1v/v)dailyfor7days.Attheendofthetreatmentperiod,tumoursareexcisedfrommice,weighedandthenfixedfor3hat4°Cwith4%paraformaldehyde,embeddedinparaffinwaxandsectioned(6µm).Apoptoticcellsare2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEidentifiedbyTUNELusingrecombinantTdt.Sectionsarethencounterstainedwitheosin.Eight×20-magnifiedfieldsfromregionscorrespondingtotheexterior,middleandinterioroftwocontrolandtwocyclopamine-treatedtumoursarechosenatrandom.WecountedthenumberofTUNEL-positivenucleimanually.Haematoxylin/eosinstainingisdone.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•NatCommun.2022Jul13;13(1):4061.•CellDeathDiffer.2021Jul;28(7):2221-2237.•PharmacolRes.2021Jan26;105460.•CellDeathDis.2019Sep12;10(9):681.•IntJNanomedicine.2017Apr20;12:3267-3280.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].PeukertS,etal.Identificationandstructure-activityrelationshipsofortho-biphenylcarboxamidesaspotentSmoothenedantagonistsinhibitingtheHedgehogsignalingpathway.BioorgMedChemLett,2009,19(2),328-331.[2].BermanDM,etal.WidespreadrequirementforHedgehogligandstimulationingrowthofdigestivetracttumours.Nature,2003,425(6960),846-851.[3].ThayerSP,etal.Hedgehogisanearlyandlatemediatorofpancreaticcancertumorigenesis.Nature,2003,425(6960),851-856.[4].MaW,etal.ReducedSmoothenedlevelrescuedAβ-inducedmemorydeficitsandneuronalinflammationinanimalmodelsofAlzheimer'sdisease.JGenetGenomics.2018May20;45(5):237-246.[5].QiWan,etal.OverexpressionofLamininα4FacilitatesProliferationandMigrationofFibroblastsinKneeArthrofibrosisbyTargetingCanonicalShh