Birabresib-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEBirabresibCat.No.:HY-15743CASNo.:202590-98-5分⼦式:C₂₅H₂₂ClN₅O₂S分⼦量:491.99作⽤靶点:EpigeneticReaderDomain作⽤通路:Epigenetics储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥49mg/mL(99.60mM)扫描⼆维码，H2O:<0.1mg/mL(insoluble)运⽤溶解⽅案计算器*"≥"meanssoluble,butsaturationunknown.获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0326mL10.1628mL20.3256mL5mM0.4065mL2.0326mL4.0651mL10mM0.2033mL1.0163mL2.0326mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(5.08mM);Clearsolution此⽅案可获得≥2.5mg/mL(5.08mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/3www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.5mg/mL(5.08mM);Suspendedsolution;Needultrasonic此⽅案可获得2.5mg/mL(5.08mM)的均匀悬浊液，悬浊液可⽤于⼝服和腹腔注射。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(5.08mM);Clearsolution此⽅案可获得≥2.5mg/mL(5.08mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。4.以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。请依序添加每种溶剂：5%DMSO40%PEG3005%Tween-8050%salineSolubility:≥3mg/mL(6.10mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Birabresib(OTX-015)⼀种有效的BRD2/3/4抑制剂，IC50值为92-112nM。IC50&TargetIC50:92-112nM(BRD2,BRD3,BRD4)[1]体外研究Birabresib(OTX-015)(500nM)exposureinducesastrongdecreaseofBRD2,BRD4andc-MYCandincreaseofHEXIM1proteins,whileBRD3expressionisunchanged.c-MYC,BRD2,BRD3,BRD4andHEXIM1mRNAlevelsdocorrelatehoweverwithviabilityfollowingexposuretoBirabresib(OTX-015)[2].Birabresib(OTX-015)(0.1,1,5μM)treatmentinducesHIV-1full-lengthtranscriptsandviraloutgrowthinrestingCD4+Tcellsfrominfectedindividualsreceivingsuppressiveantiretroviraltherapy(ART),whileexertingminimaltoxicityandeffectsonTcellactivation.Birabresib-mediatedactivationofHIV-1involvesanincreaseinCDK9occupancyandRNAPIIC-terminaldomain(CTD)phosphorylation[3].体内研究InMDA-MB-231murinexenografts,tumormassissignificantly(p<0.05)reducedbyBirabresib(OTX-015)(50mg/kg)withrespecttovehicle-treatedanimals.Birabresib(OTX-015)incombinationwith2mg/kgRAD001showsmoreeffectiveactivitythanBirabresibalone[4].PROTOCOLCellAssay[2]FortheMTTassay,cellsareseededin24-wellplatesat1×106perwellandtreatedwithBirabresib(OTX-015)(0.01nM-10μM)for72h.Cellsaretransferredto96-wellplatesandincubatedwith0.5mg/mL3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide(MTT)inthedarkat37°Cfor4h.Cellsarethenlysedwith25%sodiumdodecylsulfate(SDS)lysisbufferandabsorbanceisreadat570nmusingaMicroplateReader.Threeindependentexperimentsarerunforeachcelllineanduntreatedcellsareusedasnegativecontrols.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMicearesubcutaneouslyinjectedintherightflankwith10×106MDA-MB-231cells.WhenaveragetumorAdministration[4]weightisappr130mg,micearerandomized(nineanimals/group)tooneofthefollowingexperimental2/3www.MedChemEwww.MedChemEgroups:vehicle(forBirabresib(OTX-015),water,twicedaily,oral;forRAD001vehicle,5%Tween-80/5%polyethyleneglycol400,thriceweekly,intraperitoneal);50mg/kgBirabresib(OTX-015),twicedaily,oral;2mg/kgRAD001,thriceweekly,intraperitoneal;50mg/kgBirabresib(OTX-015)+2mg/kgRAD001,accordingtothesingleagentdosingschedules.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•Cell.2018Sep20;175(1):186-199.e19.•Hepatology.2019Jun;69(6):2502-2517.•CancerRes.2019May15;79(10):2761-2774.•CancerRes.2018Oct1;78(19):5694-5705.•ProcNatlAcadSciUSA.2019Jun25;116(26):12986-12995.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].J.KayNoel,etal.AbstractC244:DevelopmentoftheBETbromodomaininhibitorOTX015.MolCancerTherNovember201312;C244.[2].Marie-MagdelaineCoudé,etal.BETinhibitorOTX015targetsBRD2andBRD4anddecreasesc-MYCinacuteleukemiacells.Oncotarget.2015Jul10;6(19):17698–17712.[3].LuP,etal.TheBETinhibitorOTX015reactivateslatentHIV-1throughP-TEFb.SciRep.2016Apr12;6:24100[4].VázquezR,etal.ThebromodomaininhibitorOTX015(MK-8628)exertsanti-tumoractivityintriple-negativebreastcancermodelsassingleagentandincombinationwithRAD001.Oncotarget.2017Jan31;8(5):7598-7613.McePdfHeight关注MCE中