BI-2536-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEBI2536Cat.No.:HY-50698CASNo.:755038-02-9分⼦式:C₂₈H₃₉N₇O₃分⼦量:521.65作⽤靶点:Polo-likeKinase(PLK);EpigeneticReaderDomain;Apoptosis作⽤通路:CellCycle/DNADamage;Epigenetics;Apoptosis储存⽅式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性数据体外实验DMSO:65mg/mL(124.60mM;Needultrasonic)0.1MHCL:25mg/mL(47.92mM;ultrasonicandadjustpHto4withHCl)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.9170mL9.5850mL19.1699mL5mM0.3834mL1.9170mL3.8340mL10mM0.1917mL0.9585mL1.9170mL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(protectfromlight)。-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%salineSolubility:≥3.25mg/mL(6.23mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥3.25mg/mL(6.23mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.99mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性BI2536PLK1和BRD4的双抑制剂，IC50分别为0.83和25nM[1]。BI-2536抑制IFNB(IFN-β，⼲扰素β)[4]。IC50&TargetPLK1Plk2/SnkPlk3/FnkBRD40.83nM(IC50)3.5nM(IC50)9nM(IC50)25nM(IC50)体外研究Exceedinga100-foldconcentrationrangestartingat10nM,BI2536causesHeLacellstoaccumulatewitha4NDNAcontent,indicativeofacell-cycleblockineitherG2phaseormitosis.InadditiontoHeLacells,BI2536potentlyinhibitstheproliferationofapanelof32humancancercelllines,representingdiverseorganderivations(includingcarcinomasofthebreast,colon,lung,pancreas,andprostate,melanomas,andhematopoieticcancers)andvariedpatternsoftumorsuppressororoncogenemutations(includingRB1,TP53,PTEN,andKRASstatus).Thehalf-maximaleffectiveconcentration(EC50)valuesinthiscellpanelranged2-25nM,whereasaconcentrationof100nMofBI2536istypicallysufficientforinducingacompletemitoticarrest.TheproliferationofexponentiallygrowinghTERT-RPE1,humanumbilicalveinendothelialcells(HUVECs),andnormalratkidney(NRK)cellsisblockedatEC50valuesranging12-31nM,indicatingacomparablesensitivityofcyclingnontransformedcellstoBI2536[3].体内研究BI2536(40-50mg/kg,i.v.)blocksthegrowthofhumancancerxenograftsinimmunodeficient,nu/numice.Consecutivecyclesof40-50mg/kgBI2536giveni.v.onceortwiceperweekarefoundtobehighlyefficaciousindiversexenograftmodels,suchastheHCT116coloncancerwithcompletetumorsuppressionwiththetwiceperweekschedule(treatedversusthecontrol(T/C)value0.3%)andaT/Cvalueof16%withonceperweektreatment;bothschedulesarewell-tolerated,asjudgedbyclinicalsignsandabsenceofmajorbody-weightchanges[3].PROTOCOLCellAssay[3]CellproliferationassaysareperformedbyincubationinthepresenceofvariousconcentrationsofBI2536(10nM-1μM)for72hr,andcellgrowthisassessedbythemeasurementofAlamarBluedyeconversioninafluorescencespectrophotometer.Effectiveconcentrationsatwhichcellulargrowthisinhibitedby50%(EC50)areextrapolatedfromthedose-responsecurvefit[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]FemaleBomTac:NMRI-Foxn1numicearegraftedsubcutaneouslywithHCT116colon-carcinoma,NCI-H460,orA549lung-carcinomacellsbysubcutaneousinjection,respectively,of2×106,1×106,and1×107cellsintotheflankofeachmouse.Whentumorsreachedavolumeofapproximately50mm3,animalsare2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEpair-matchedintotreatmentandcontrolgroupsoftenmiceeach.Inregressionexperiments,treatmentisnotinitiateduntilthemeantumorvolumereached500mm3.BI2536isinjectedintravenouslyintothetailveinattheindicateddoseandschedule.Theadministrationvolumeis10mLperkgbodyweight.Tumorvolumesaredeterminedthreetimesaweekwithacaliper.Theresultsareconvertedtotumorvolume(mm3)bythefollowingformula:length×width2×π/6.Theweightofthemiceisdeterminedasanindicatoroftolerabilityonthesamedays.Forstatisticalanalysis,thetreatmentgroupiscomparedwiththevehiclecontrolgroupinaone-sided(decreasing)exactWilcoxontest.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•SciTranslMed.2018Jul18;10(450).pii:eaaq1093.•NatCommun.2018Oct15;9(1):4275.•NatCommun.2017Nov22;8(1):1701.•CancerRes.2022Feb15;82(4):681-694.•CancerRes.2017Sep15;77(18):4785-4796.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].LénártP,etal.TheSmall-MoleculeInhibitorBI2536RevealsNovelInsightsintoMitoticRolesofPolo-likeKinase1.CurrBiol.2007Feb20;17(4):304-15.[2].ChenL,etal.BRD4Structure-ActivityRelationshipsofDualPLK1Kinase/BRD4BromodomainInhibitorBI-2536.ACSMedChemLett.2015May18;6(7):764-9.[3].SteegmaierM,etal.BI2536,aPotentandSelectiveInhibitorofPolo-likeKinase1,InhibitsTumorGrowthInVivo.CurrentBiology(2007),17(4),316-322.[4].MalikN,etal.SuppressionofIFNβgenetranscriptionbyinhibitorsofbromodomainan