Debio-0932-CUDC-305-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEDebio0932Cat.No.:HY-13469CASNo.:1061318-81-7Synonyms:CUDC-305分⼦式:C₂₂H₃₀N₆O₂S分⼦量:442.58作⽤靶点:HSP作⽤通路:CellCycle/DNADamage;MetabolicEnzyme/Protease储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:75mg/mL(169.46mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.2595mL11.2974mL22.5948mL5mM0.4519mL2.2595mL4.5190mL10mM0.2259mL1.1297mL2.2595mL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。-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(5.65mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.65mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.65mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Debio0932(CUDC-305)⼀种可⼝服的HSP90抑制剂，对HSP90α和HSP90β的IC50值分别为100和103nM[1]。IC50&TargetHSP90αHSP90β100nM(IC50)103nM(IC50)体外研究Debio0932isanorallyactiveHSP90inhibitor,withIC50sof100and103nMforHSP90αandHSP90β,respectively.Debio0932(CUDC-305)bindstothetumorHSP90complexwithameanIC50of48.8nM.Debio0932(1μM)promotesdegradationofmultipleHSP90clientproteinsincancercelllines.Debio0932alsoshowsinhibitoryactivitiesagainsttheproliferationof40cancercelllines(containing34solidand6hematologictumor-derivedlines)withanIC50rangingfrom40to900nM(meanIC50,220nM)[1].Debio0932stronglybindstocancer-derivedHSP90complexwithanIC50of61.2nMinH1975cellsand74.2nMinH1993cells,respectively.Debio0932(CUDC-305,1μM)durablyinducesoncoproteindegradationinNSCLCcelllineswithmutationsthatcanconferresistancetoerlotinib[3].体内研究Debio0932(CUDC-305,30mg/kg,p.o.)exhibitsfavorablepharmacokineticprofilesintumor-bearingnudemice.Debio0932(160mg/kg,p.o.)causesdegradationofHSP90clientproteins,suppressestumorgrowth,andalsoprolongssurvivalinvariousanimalmodelsofU87MGglioblastoma.Debio0932(40,80,or160mg/kg,p.o.)alsodose-dependentlyinhibitstumorgrowthintheU87MGs.c.tumormodelbyevery-other-day(q2d)dosing[1].Debio0932(80mg/kg,p.o.)significantlyalleviatespsoriasisbyday11anddecreasesepidermalthicknessinpsoriasisxenografttransplantationmodel[2].Debio0932(CUDC-305)isabletocrosstheblood-brainbarrier.Debio0932(80,120,and160mg/kg,p.o.)showsdose-dependentinhibitionoftumorgrowthintheH1975subcutaneoustumormodel.Debio0932(160mg/kg,p.o.)alsopromotesantitumoractivityintheerlotinib-resistantH1975subcutaneoustumormodel[3].PROTOCOLCellAssay[1]Humancancercelllinesareplatedat5,000to10,000perwellin96-wellplateswithculturemedium.Thecellsarethenincubatedwithcompounds(Debio0932)atvariousconcentrationsfor120h.GrowthinhibitionisassessedbyATPcontentassayusingtheATPlitekit.Briefly,a25-μLcelllysissolutionisaddedtothe50-μLphenolred-freeculturemediumperwelltolysecellsandstabilizeATP.Then25-μLsubstratesolutionsareaddedtothewells,andsubsequently,luminescenceismeasuredwithaTopCountliquidscintillationanalyzer.Valuesareexpressedasapercentagerelativetothoseobtainedinuntreatedcontrols.IC50valuesarecalculatedusingPRISMsoftwarewithsigmoidaldose-responsecurvefitting[1].2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEMCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalWhentumorsareestablishedafterimplantation,animalswithpropertumorsizearerandomlyassignedintoAdministration[1]differentgroups.Debio0932isformulatedin30%Captisolanddeliveredbyoralgavagebasedonthebodyweightofeachindividualanimal.Thecontrolgroupistreatedwithvehicle(30%Captisol)usingthesamedosingparadigm.Incombinationstudies,paclitaxelorcamptothecin-11isdilutedin0.9%normalsalineandinjectedi.p.twiceweekly[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•EMBOMolMed.2022Feb17;e14552.•ClinTranslMed.2022Jul;12(7):e961.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].BaoR,etal.CUDC-305,anovelsyntheticHSP90inhibitorwithuniquepharmacologicpropertiesforcancertherapy.ClinCancerRes.2009Jun15;15(12):4046-57.[2].StenderupK,etal.Debio0932,aneworalHsp90inhibitor,alleviatespsoriasisinaxenografttransplantationmodel.ActaDermVenereol.2014Nov;94(6):672-6.[3].BaoR,etal.Targetingheatshockprotein90withCUDC-305overcomeserlotinibresistanceinnon-smallcelllung