Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEBI2536Cat.No.:HY-50698CASNo.:755038-02-9分?式:C??H??N?O?分?量:521.65作?靶點(diǎn):Polo-likeKinase(PLK);EpigeneticReaderDomain;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲(chǔ)存?式:4°C,protectfromlight*Insolvent:-80°C,6months;-20°C,1month(protectfrom

light)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:65mg/mL(124.60mM;Needultrasonic)0.1MHCL:25mg/mL(47.92mM;ultrasonicandadjustpHto4withHCl)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9170mL9.5850mL19.1699mL5mM0.3834mL1.9170mL3.8340mL10mM0.1917mL0.9585mL1.9170mL請(qǐng)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(chǔ)備液；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month(protectfromlight)。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)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(chǔ)備液可以根據(jù)儲(chǔ)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(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥3.25mg/mL(6.23mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥3.25mg/mL(6.23mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(3.99mM);ClearsolutionBIOLOGICALACTIVITY?物活性BI2536PLK1和BRD4的雙抑制劑，IC50分別為0.83和25nM[1]。BI-2536抑制IFNB(IFN-β，?擾素β)[4]。IC50&TargetPLK1Plk2/SnkPlk3/FnkBRD40.83nM(IC50)3.5nM(IC50)9nM(IC50)25nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEpair-matchedintotreatmentandcontrolgroupsoftenmiceeach.Inregressionexperiments,treatmentisnotinitiateduntilthemeantumorvolumereached500mm3.BI2536isinjectedintravenouslyintothetailveinattheindicateddoseandschedule.Theadministrationvolumeis10mLperkgbodyweight.Tumorvolumesaredeterminedthreetimesaweekwithacaliper.Theresultsareconvertedtotumorvolume(mm3)bythefollowingformula:length×width2×π/6.Theweightofthemiceisdeterminedasanindicatoroftolerabilityonthesamedays.Forstatisticalanalysis,thetreatmentgroupiscomparedwiththevehiclecontrolgroupinaone-sided(decreasing)exactWilcoxontest.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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