CBL0137-hydrochloride-Curaxin-137-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemECBL0137hydrochlorideCat.No.:HY-18935ACASNo.:1197397-89-9Synonyms:Curaxin-137hydrochloride;CBL-C137hydrochloride分⼦式:C₂₁H₂₅ClN₂O₂分⼦量:372.89作⽤靶点:MDM-2/p53;NF-κB作⽤通路:Apoptosis;NF-κB储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验DMSO:33.33mg/mL(89.38mM;Needultrasonic)H2O:10mg/mL(26.82mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.6818mL13.4088mL26.8176mL5mM0.5364mL2.6818mL5.3635mL10mM0.2682mL1.3409mL2.6818mL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(sealedstorage,awayfrommoisture)。-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%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.5mg/mL(6.70mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.70mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性CBL0137hydrochloride组蛋⽩分⼦伴侣FACT的抑制剂。CBL0137hydrochlorideye也可以激活p53并抑制NF-κB，对于它们的EC50值分别为0.37和0.47μM。IC50&TargetNF-κBp530.47μM(IC50)0.37μM(IC50)体外研究TreatmentwithCBL0137hydrochlorideleadstocompleteabsenceoflivingcellsatconcentrationsabove2.5μM.CBL0137hydrochloridecausesagreaterreductioninthenumberofcoloniesformedofnotonlyMiaPaCa-2cellswhencombineswithgemcitabine,butalsogemcitabine-resistantPANC-1cells.TreatmentofhumanpancreaticcancercellswithCBL0137hydrochlorideresultsinadosedependentreductionofproteinandmRNAlevelsofRRM1andRRM2[1].体内研究TheCBL0137hydrochloridemonotherapygroupandtheCBL0137hydrochloride-gemcitabinecombinationgroupsamplesshowlargenecroticfields,numerousapoptoticbodiesandlossoftumorcells.Sub-optimaldosesof50to60mg/kgCBL0137hydrochloridecausessimilarenhancementofgemcitabineantitumoractivityasthatproducedbythemaximumtolerateddose(MTD)of90mg/kgasindicatedbythelackofstatisticallysignificantdifferencesamongthecombinationgroups.CBL0137hydrochlorideinhibitsFACTfunctionthroughdepletionofthepoolofactiveFACTinvolvedintranscriptionelongation[1].CBL0137hydrochloride,givenbyoralgavageatanontoxicdoseof30mg/kgperdayona5dayson/2daysoffschedule,suppressestumorgrowthinxenograftsofcolon(DLD-1),renalcellcarcinoma(Caki-1),andmelanoma(Mel-7)tumorcelllinesandtransplantedsurgicalsamplesfrompatientswithpancreaticductaladenocarcinoma[2].PROTOCOLKinaseAssay[1]MiaPaca2andBxPC-3cellsaretreatedwithCBL0137hydrochloridefor4or24h.Cellsareharvestedin1×CellCultureLysisReagentcontainingproteaseandphosphataseinhibitors.Lysates5to20μgareseparatedonSDSgelsandtransferredtoPVDFmembranes.BlotsareprobedwithantibodiesspecificforSSRP1,SPT16,RRM1,andRRM2.GAPDHisusedasaloadingcontrol.ProteinsarevisualizedusingECLkit[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.CellAssay[1]CellsareresuspendedinserumfreeDulbecco'sModifiedEagleMedium(DMEM)andtreatedwithdifferentconcentrationsofCBL0137hydrochloridefor1h.Afterthat105cellsfromeachtreatmentconditionareplatedin3wellsof6-wellplatein2mLofserum-freeDMEM/F12mediumsupplementedwith0.4%BSA,0.2×B27,10ng/mLrecombinantEGFandcontaining0.25%agarose.103cellsfromeachtreatmentconditionare2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEplatedin3wellsof6-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/kgCBL0137hydrochloridein100mg/mLcaptisoli.v.deliveredviatailveinonceperweek,3)10to20mg/kgCBL0137hydrochloridep.o.viaoralgavage,5dayson/2daysoff.Tumormeasurementisdonewithdigitalcalipers.TumorvolumeiscalculatedusingtheequationL×W2/2whereListhelongestdimensionandWisthedimensionperpendiculartoW.Micearefolloweduntilatleastonetumorpermousereached1000mm3or90daysfromstartoftreatment,whichevercomesfirst[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.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.MedChemEREFERENCES[1].BurkhartC,etal.CuraxinCBL0137eradicatesdrugresistantcancerstemcellsandpotentiatesefficacyofgemcitabineinpreclinicalmodelsofpancreaticcancer.Oncotarget.2014Nov30;5(22):11038-53.[2].GasparianAV,etal.Curaxins:anticancercompoundsthatsimultaneouslysuppressNF-κBan