EDO-S101-Tinostamustine-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEEDO-S101Cat.No.:HY-101780CASNo.:1236199-60-2Synonyms:Tinostamustine分⼦式:C₁₉H₂₈Cl₂N₄O₂分⼦量:415.36作⽤靶点:HDAC作⽤通路:CellCycle/DNADamage;Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:100mg/mL(240.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.4076mL12.0378mL24.0755mL5mM0.4815mL2.4076mL4.8151mL10mM0.2408mL1.2038mL2.4076mL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:2.5mg/mL(6.02mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性EDO-S101(Tinostamustine)HDAC的⼴谱抑制剂；抑制HDAC1，HDAC2和HDAC3的IC50值分别为6nM，9nM，9nM和25nM[1]。IC50&TargetHDAC6HDAC1HDAC2HDAC36nM(IC50)9nM(IC50)9nM(IC50)25nM(IC50)HDAC10HDAC872nM(IC50)107nM(IC50)体外研究EDOS101inhibitsHDACactivityinratperipheralbloodmononuclearcells(PBMCs)inacellularassaybyapproximately90%onehourafterdosingwith10mg/kgi.v.HDACinhibitioninPBMCscouldnotbeincreasedwithhigherdosesupto50mg/kg.EDO-S101triggersapoptosisandshowsstrongantitumoractivityinHL60andDaudicells.InitialinvitroexperimentsinHL60cellsshowsanactivationoftheintrinsicpathwayofapoptosiswithcleavageofcaspases3,9andPARPandamarkedreductionofanti-apoptoticproteinsXIAPandMcl-1[1].体内研究IntracellularHDACinhibitionofEDO-S101,whichoccursrapidlyafterdosingisatmaximumactivityalreadyatthelowestdoseof10mg/kgandlastsforabout12-16hours.ExposuretoEDO-S101causesastrongDNArepairresponseevidencedbyactivationofpH2AXandp53intumorstakenfrommicebearingsubcutaneoushumanBurkitt’slymphoma.TumorsofBLrapidlyshrinkorarecompletelyeradicatedafteri.v.administrationofEDO-S101[1].PROTOCOLKinaseAssay[1]EDO-S101isdissolvedinDMSOandaddedtotheassaybuffersolution.EDO-S101dilutionsof5μLofeachdilutionisaddedto50μLofthereactionmixtureincludingtheFluordeLyssubstrateandalloftheenzymaticreactionsareconductedinduplicateat37°Cfor30minutes.Afterenzymaticreactions,50μLof2xHDACdeveloperisaddedtoeachwellandfluorescenceintensityismeasured[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalRats:ThedurationofHDACinhibitionisassessedin12femaleratsafterreceivingasingledoseofeitherAdministration[1]vehicleorEDO-S101(25mg/kg).BloodsamplesfromEDO-S101treatedratsarecollected1hr,3hr,6hr,16hrand24hrpostdosing(n=2pertimepoint).Bloodsamplefromvehicletreatedrats(n=2)arecollected24hrpostdosing[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE•ActaPharmacolSin.2021Apr13.•IntJMolSci.2022Apr2;23(7):3980.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].MehrlingT,etal.TheAlkylating-HDACInhibitionFusionPrinciple:TakingChemotherapytotheNextLevelwiththeFirstinClassMoleculeEDO-S101.AnticancerAgentsMedChem.2016;16(1):20-8.McePdfHeightCaution:Product