Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAlvespimycinCat.No.:HY-10389CASNo.:467214-20-6Synonyms:17-DMAG;NSC707545分?式:C??H??N?O?分?量:616.75作?靶點(diǎn):HSP作?通路:CellCycle/DNADamage;MetabolicEnzyme/Protease儲(chǔ)存?式:PleasestoretheproductundertherecommendedconditionsintheCertificateofAnalysis.BIOLOGICALACTIVITY?物活性Alvespimycin(17-DMAG)?種有效的Hsp90抑制劑，結(jié)合到Hsp90，EC50為62±29nM。IC50&TargetHSP90GRP9462nM(EC50)65nM(EC50)體外研究Alvespimycin(17-DMAG)isapotentinhibitorofHsp90,bindingtoHsp90withanEC50of62nM.Alvespimycin(17-DMAG)inhibitsthegrowthofthehumancancercelllinesSKBR3andSKOV3,whichoverexpressHsp90clientproteinHer2,andcausesdown-regulationofHer2aswellasinductionofHsp70consistentwithHsp90inhibition,forHer2degradationwithEC50of8±4nMand46±24nMinSKBR3andSKOV3cells,respectively;forHsp70inductionwithEC50of4±2nMand14±7nMinSKBR3andSKOV3cells,respectively[1].Comparedwiththevehiclecontrol,Alvespimycin(17-DMAG)dose-dependentapoptosis(P[2].體內(nèi)研究Thetumorsaregrownfortwomonthsbeforethestartofi.p.injectionseveryfourdaysoveronemonthwith0,50,100and200mg/kgdipalmitoyl-radicicolor0,5,10and20mg/kgAlvespimycin(17-DMAG).Despitesampleheterogeneity,theHSP90inhibitor-treatedanimalshavesignificantlylowertumourvolumesthanthevehiclecontrol-treatedanimals.HSP90inhibitorshavebeenshowntocauselivertoxicityinananimalmodelofgastrointestinalcancer.Nevertheless,thereductionintumorsizeusingdipalmitoyl-radicicolisstatisticallysignificantat100mg/kg,whileAlvespimycin(17-DMAG)ateither10or20mg/kgelicitsasignificantreductionintumorsize[3].1/2MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEPROTOCOLCellAssay[2]MTTassaysareperformedtodeterminecytotoxicity.Atotalof1×106CD19-selectedBcellsfromCLLpatientsareincubatedfor24or48hoursinAlvespimycin,17-AAG,orvehicle.MTTreagentisthenadded,andplatesareincubatedforanadditional24hoursbeforespectrophotometricmeasurement.ApoptosisisdeterminedbystainingwithannexinV-fluoresceinisothiocyanateandpropidiumiodide(PI).Afterexposuretodrugs,cellsarewashedwithphosphate-bufferedsalineandstainedin1timebindingbuffer.Celldeathisassessedbyflowcytometry.DataareanalyzedwiththeSystemIIsoftwarepackage.Atotalof10000cellsarecountedforeachsample.MitochondrialmembranepotentialchangesareassessedbystainingwiththelipophiliccationicdyeJC-1andanalysisbyflowcytometry[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]Administration[3]YoungmaleCB-17/IcrHsd-Prkdc-SCIDmiceareused.Recombinantxenograftsaremadebymixing1×105BPH1cellsand2.5×105CAFpergraftincollagensolution,allowedtogel,coveredwithmediumandculturedovernight.Tumorsareallowedtoformovereightweeks,andthentreatedforfourweekswiththreedifferentdosesofdipalmitoyl-radicicol(50,100and200mg/kg)andAlvespimycin(5,10and20mg/kg)viaintraperitonealinjectionsofcompoundsinsesameoileveryfourdays.After12weeksintotal,themicearesacrificed,theirkidneysresected,graftscutinhalfandphotographedbeforeprocessingforhistology.Graftdimensionsaremeasuredandtheresultanttumourvolumeiscalculatedusingtheformula;volume=width×length×depth×π/6.Thisformularepresentsaconservativeapproachtoevaluatetumourvolumes,asitunderstatesthevolumeoflarge,invasivetumourscomparedwithsmaller,non-invasivetumours.Resectedgraftsarefixedin10%formalin,embeddedinparaffinandprocessedforimmunohistochemistry.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?NatCommun.2021Jul22;12(1):4457.?Theranostics.2020Jul9;10(18):8415-8429.?Theranostics.2020Jul9;10(18):8415-8429.?PharmacolRes.2020Jan;151:104512.?CellDeathDis.2022Jan21;13(1):73.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].GeJ,etal.Design,synthesis,andbiologicalevaluationofhydroquinonederivativesof17-amino-17-demethoxygeldanamycinaspotent,water-solubleinhibitorsofHsp90.JMedChem.2006Jul27;49(15):4606-15.[2].HertleinE,etal.17-DMAGtargetsthenuclearfactor-kappaBfamilyofproteinstoinduceapoptosisinchroniclymphocyticleukemia:clinicalimplicationsofHSP90inhibition.Blood.2010Jul8;116(1):45-53.[3].HenkeA,etal.ReducedContractilityandMotilityofProstaticCancer-AssociatedFibroblastsafterInhibitionofHeatShockProtein90.Cancers(Basel).2016Aug24;8(9).pii:E77.McePdfHeight2/2Masterof