BETd-260-ZBC-260-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBETd-260Cat.No.:HY-101519CASNo.:2093388-62-4Synonyms:ZBC260分⼦式:C₄₃H₄₆N₁₀O₆分⼦量:798.89作⽤靶点:PROTACs;EpigeneticReaderDomain;Apoptosis作⽤通路:PROTAC;Epigenetics;Apoptosis储存⽅式:-80°C,protectfromlight,storedundernitrogen溶解性数据体外实验DMSO:25mg/mL(31.29mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.2517mL6.2587mL12.5174mL5mM0.2503mL1.2517mL2.5035mL10mM0.1252mL0.6259mL1.2517mL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(protectfromlight,storedundernitrogen)。-80°C储存时，请在6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%salineSolubility:≥0.83mg/mL(1.04mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥0.83mg/mL(1.04mM);Clearsolution1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEBIOLOGICALACTIVITY⽣物活性BETd-260(ZBC260)由Cereblon配体和BET配体相连的PROTAC，在⽩⾎病细胞RS4;11中，在30pM的低浓度下，能够降低BRD4蛋⽩活性。BETd-260能显著抑制肝细胞癌HCC细胞的活性并诱导细胞凋亡(apoptosis)。IC50&TargetBRD4BRD2BRD350)30-100pM(IC50)30-100pM(IC50)体外研究BETd-260(ZBC260;Compound23)iscapableofinducingdegradationofBRD2,BRD3,andBRD4proteinsat30–100pMintheRS4;11leukemiacells.BETd-260showsinhibitoryactivityagainstthegrowthofRS4;11leukemiacellsandMOLM-13cellswithIC50sof51pMand2.2nM,respectively,andinducesapoptosisinbothRS4;11andMOLM-13celllinesat3-10nM[1].BETd-260reciprocallymodulatestheexpressionofseveralapoptoticgenesinHCCcells,i.e.,suppressingtheexpressionofanti-apoptoticMcl-1,Bcl-2,c-Myc,andXIAP,whereasincreasingtheexpressionofpro-apoptoticBad[2].体内研究BETd-260(5mg/kg,i.v.,everyotherday,thriceaweekfor3weeks)causesrapidtumorregressionwithamaximumof>90%regressioninmicebearingRS4;11xenografttumors,andwithnobodyweightlossorothersignsoftoxicityinmice.BETd-260(5mg/kg,i.v.)degradestheBRD2,BRD3,andBRD4proteinsformorethan24h,withrobustcleavageofPARPandcaspase-3,andstrongdown-regulationofc-MycproteininRS4;11xenograftmicemodel[1].PROTOCOLCellAssay[1]Incellgrowthexperiments,cellsareseededin96-wellcellcultureplatesatadensityof10000−20000cells/wellin100μLofculturemedium.BETd-260isseriallydilutedintheappropriatemedium,and100μLofthedilutedsolutioncontainingBETd-260isaddedtotheappropriatewellsofthecellplate.AfteradditionofBETd-260,thecellsareincubatedfor4daysat37°Cinanatmosphereof5%CO2.Cellgrowthisevaluatedbyalactatedehydrogenase-basedWST-8assayusingamultimodemicroplatereader.TheWST-8reagentisaddedtotheplate,incubatedforatleast1h,andreadat450nm.ThereadingsarenormalizedtotheDMSO-treatedcells,andtheIC50iscalculatedbynonlinearregressionanalysisusingGraphPadPrism6software[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]Todevelopxenografttumors,5×106RS4;11cellswith50%Matrigelareinjectedsubcutaneouslyonthedorsalsideofseverecombinedimmunodeficient(SCID)mice,onetumorpermouse.Whentumorsreachappr100mm3,micearerandomlyassignedtoBETd-260treatmentandvehiclecontrolgroups.Animalsaremonitoreddailyforanysignsoftoxicityandweighed2-3timesperweekduringthetreatmentandweighedatleastweeklyafterBETd-260treatmentend.Tumorsizeismeasured2-3timesperweekbyelectroniccalipersduringthetreatmentperiodandatleastweeklyafterthetreatmentisend.Tumorvolumeis2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEcalculatedasV=LW2/2,whereListhelengthandWisthewidthofthetumor[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].ZhouB,etal.DiscoveryofaSmall-MoleculeDegraderofBromodomainandExtra-Terminal(BET)ProteinswithPicomolarCellularPotenciesandCapableofAchievingTumorRegression.JMedChem.2018Jan25;61(2):462-481.[2].ZhangH,etal.TargetingBETProteinsWithaPROTACMoleculeElicitsPotentAnticancerActivityinHCCCells.FrontOncol.2020;9:1471.Publish