Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEEDO-S101Cat.No.:HY-101780CASNo.:1236199-60-2Synonyms:Tinostamustine分?式:C??H??Cl?N?O?分?量:415.36作?靶點(diǎn):HDAC作?通路:CellCycle/DNADamage;Epigenetics儲存?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(240.76mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.4076mL12.0378mL24.0755mL5mM0.4815mL2.4076mL4.8151mL10mM0.2408mL1.2038mL2.4076mL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(shí)，請?jiān)?個(gè)?內(nèi)使?，-20°C儲存時(shí)，請?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請根據(jù)您的實(shí)驗(yàn)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(shí)驗(yàn)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(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:2.5mg/mL(6.02mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性EDO-S101(Tinostamustine)HDAC的?譜抑制劑；抑制HDAC1，HDAC2和HDAC3的IC50值分別為6nM，9nM，9nM和25nM[1]。IC50&TargetHDAC6HDAC1HDAC2HDAC36nM(IC50)9nM(IC50)9nM(IC50)25nM(IC50)HDAC10HDAC872nM(IC50)107nM(IC50)體外研究EDOS101inhibitsHDACactivityinratperipheralbloodmononuclearcells(PBMCs)inacellularassaybyapproximately90%onehourafterdosingwith10mg/kgi.v.HDACinhibitioninPBMCscouldnotbeincreasedwithhigherdosesupto50mg/kg.EDO-S101triggersapoptosisandshowsstrongantitumoractivityinHL60andDaudicells.InitialinvitroexperimentsinHL60cellsshowsanactivationoftheintrinsicpathwayofapoptosiswithcleavageofcaspases3,9andPARPandamarkedreductionofanti-apoptoticproteinsXIAPandMcl-1[1].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)2/3MasterofBioactiveMolecules—您?邊的抑制劑?師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