CBL0137-Curaxin-137-DataSheet-生命科学试剂-MCE

Hotline:400-820-3792Inhibitors • ScreeningLibraries • Proteinswww.MedChemECBL0137Cat.No.:HY-18935CASNo.:1197996-80-7Synonyms:Curaxin137;CBL-C137分子式:C₂₁H₂₄N₂O₂分子量:336.43作用靶点:HistoneAcetyltransferase;MDM-2/p53;MDM-2/p53;NF-κB作用通路:Epigenetics;Apoptosis;NF-κB储存方式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY生物活性CBL0137是一种curaxin化合物，是一种组蛋白伴侣促进染色质转录(FACT)抑制剂。CBL0137下调NF-?B并激活p53。CBL0137可恢复组蛋白H3乙酰化和三甲基化。CBL0137是一种抗癌剂。CBL0137诱导癌细胞凋亡(apoptosis)。体外研究TreatmentwithCBL-0137leadstocompleteabsenceoflivingcellsatconcentrationsabove2.5μM.CBL-0137causesagreaterreductioninthenumberofcoloniesformedofnotonlyMiaPaCa-2cellswhencombinedwithgemcitabine,butalsogemcitabine-resistantPANC-1cells.TreatmentofhumanpancreaticcancercellswithCBL-0137resultsinadosedependentreductionofproteinandmRNAlevelsofRRM1andRRM2.CBL-0137isabletopreventgemcitabineinducedexpressionofRRM1andRRM2onmRNAandproteinlevels[1].体内研究TheCBL-0137monotherapygroupandtheCBL-0137-gemcitabinecombinationgroupsamplesshowlargenecroticfields,numerousapoptoticbodiesandlossoftumorcells.Sub-optimaldosesof50to60mg/kgCBL-0137causessimilarenhancementofgemcitabineantitumoractivityasthatproducedbythemaximumtolerateddose(MTD)of90mg/kgasindicatedbythelackofstatisticallysignificantdifferencesamongthecombinationgroups.CBL0137hydrochlorideinhibitsFACTfunctionthroughdepletionofthepoolofactiveFACTinvolvedintranscriptionelongation[1].CBL-0137,givenbyoralgavageatanontoxicdoseof30mg/kgperdayona5dayson/2daysoffschedule,suppressestumorgrowthinxenograftsofcolon(DLD-1),renalcellcarcinoma(Caki-1),andmelanoma(Mel-7)tumorcelllinesandtransplantedsurgicalsamplesfrompatientswithpancreaticductaladenocarcinoma[2].1/2 MasterofBioactiveMolecules—您身边的抑制剂大师www.MedChemEPROTOCOLKinaseAssay[1]MiaPaca2andBxPC-3cellsaretreatedwithCBL-0137for4or24h.Cellsareharvestedin1×CellCultureLysisReagentcontainingproteaseandphosphataseinhibitors.Lysates5to20μgareseparatedonSDSgelsandtransferredtoPVDFmembranes.BlotsareprobedwithantibodiesspecificforSSRP1,SPT16,RRM1,andRRM2.GAPDHisusedasaloadingcontrol.ProteinsarevisualizedusingECLkit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]CellsareresuspendedinserumfreeDulbecco'sModifiedEagleMedium(DMEM)andtreatedwithdifferentconcentrationsofCBL-0137for1h.Afterthat105fromeachtreatmentconditionareplatedin3wellsof6-wellplatein2mLofserum-freeDMEM/F12mediumsupplementedwith0.4%BSA,0.2×B27,10ng/mLrecombinantEGFandcontaining0.25%agarose.103cellsfromeachtreatmentconditionareplatedin3wellsof6-wellplateinregularFBScontainingmedium.Coloniesarecountedusinginvertedmicroscope7to15daysafterplating[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.Animal10-weekoldfemaleathymicnudemice(n=8pertreatmentgroup)aredeeplyanesthetizedwithAdministration[1]ketamine/xylazine.Usinglaparotomy,2×106PANC-1cellsareinoculatedintothetailofthepancreasofeachmouse.Twoweeksfollowinginoculation(tumorpresenceconfirmedbyultrasound),treatmentcommenced.Thefollowingregimensareused:1)vehicles,100mg/kgcaptisoli.v.andsterilewaterviagavage,2)50to90mg/kgCBL-0137in100mg/mLcaptisoli.v.deliveredviatailveinonceperweek,3)10to20mg/kgCBL-0137p.o.viaoralgavage,5dayson/2daysoff,4).Tumormeasurementisdonewithdigitalcalipers.TumorvolumeiscalculatedusingtheequationL×W2/2whereListhelongestdimensionandWisthedimensionperpendiculartoW.Micearefolloweduntilatleastonetumorpermousereached1000mm3or90daysfromstartoftreatment,whichevercomesfirst[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.客户使用本产品发表的科研文献CancerRes.2021Jun1;81(11):3105-3120.CellDeathDis.2020Dec2;11(12):1029.Oncogene.2022Nov10.Seemorecustomervalidationsonwww.MedChemEREFERENCESBaroneTA,etal.AnticancerdrugcandidateCBL0137,whichinhibitshistonechaperoneFACT,isefficaciousinpreclinicalorthotopicmodelsoftemozolomide-responsiveand-resistantglioblastoma.NeuroOncol.2017Feb1;19(2):186-196.hBurkhartC,etal.CuraxinCBL0137eradicatesdrugresistantcancerstemcellsandpotentiatesefficacyofgemcitabineinpreclinicalmodelsofpancreaticcancer.Oncotarget.2014Nov30;5(22):11038-53.EhtedaA,etal.DualtargetingoftheepigenomeviaFACTcomplexandhistonedeacetylaseisapotenttreatmentstrategyforDIPG.CellRep.2021Apr13;35(2):108994.McePdfHeight2/2 Mas