Fenretinide-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•Agonists•ScreeningLibrarieswww.MedChemEFenretinideCat.No.:HY-15373CASNo.:65646-68-6分⼦式:C₂₆H₃₃NO₂分⼦量:391.55作⽤靶点:RAR/RXR;Autophagy作⽤通路:MetabolicEnzyme/Protease;Autophagy储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥130mg/mL(332.01mM)扫描⼆维码，*"≥"meanssoluble,butsaturationunknown.运⽤溶解⽅案计算器获得适合您实验体系的溶解⽅案MassSolvent1mg5mg10mgConcentration制备储备液1mM2.5540mL12.7698mL25.5395mL5mM0.5108mL2.5540mL5.1079mL10mM0.2554mL1.2770mL2.5540mL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，并请注意储备液的保存⽅式和期限。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%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(6.38mM);Clearsolution此⽅案可获得≥2.5mg/mL(6.38mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到400μLPEG300中，混合均匀；向上述体系中加⼊50μLTween-80，混合均匀；然后继续加⼊450μL⽣理盐⽔定容⾄1mL。1/4www.MedChemEwww.MedChemE2.请依序添加每种溶剂：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.38mM);Clearsolution此⽅案可获得≥2.5mg/mL(6.38mM，饱和度未知)的澄溶液。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL20%的SBE-β-CD⽣理盐⽔⽔溶3.液中，混合均匀。请依序添加每种溶剂：10%DMSO90%cornoilSolubility:≥2.5mg/mL(6.38mM);Clearsolution此⽅案可获得≥2.5mg/mL(6.38mM，饱和度未知)的澄溶液，此⽅案不适⽤于实验周期在半个⽉以上的实验。以1mL⼯作液为例，取100μL25.0mg/mL的澄DMSO储备液加到900μL⽟⽶油中，混合均匀。BIOLOGICALACTIVITY⽣物活性Fenretinide(4-HPR)⼀种合成的类维⽣素A衍⽣物，能够结合视酸受体(RAR)诱导细胞死亡。体外研究Fenretinide(4-HPR)exertsnotjustacutebutalsolongtermantitumoractivityinselectedT-ALLcelllines.FenretinideinhibitsDESactivityinCCRF-CEMleukemiacellsinadoseandtimedependentmanner,leadingtoaconcomitantincreaseoftheendogenouscellulardhCercontent.Fenretinide(3μM)-induceddhCeraccumulationinbothCCRF-CEMandJurkatcells[1].Ceramideinhibitionwithfenretinideprotectsinsulinsignaling.Fenretinidepreventslipid-inducedreductionsininsulin-stimulatedglucoseuptake[2].FenretinideinhibitsOVCAR-5cellproliferationandviabilityatconcentrationshigherthan1microM,with70-90%growthinhibitionat10microM.Fenretinide(1microM)significantlyinhibitsOVCAR-5invasionafter3dayspreincubation.Endothelialcellstreatedwith1microM4-HPRfailstoformtubes,butformssmallcellularaggregates[4].体内研究Fenretinide(4-HPR)(10mg/kg,i.p.)selectivelyinhibitsceramideaccumulationHFD-fedmaleC57Bl/6mice.Fenretinidetreatmentimprovesglucosetoleranceandinsulinsensitivityasdeterminedbybothglucoseandinsulintolerancetests[2].Additionof25mg/kgketoconazoletoFenretinideinNOD/SCIDmiceincreased4-HPRplasmalevels[3].PROTOCOLCellAssay[1]StandardXTTassayisusedtodeterminecellviability.Forfenretinide-onlytreatments,cellsareplatedin96-wellplatesat750,000cells/mLand100μL/well.After4h,treatmentsareaddedon50μL/wellobtainingafinaldensityof500,000cells/mLandfinalvolumeof150μL/well.Fourreplicatesareusedperexperimentalcondition.XTTreagentmixtureisadded4hbeforetheendofselectedtreatmentperiodandabsorbanceat490nmisdeterminedpereachwell.Aslightlymodifiedprotocolisusedforanalysisoftheeffectofmyriocin(finalconcentrationof100nM)orantioxidantonFenretinidetreatment.Briefly,cellsareseededon60mmculturedishesandmyriocinorantioxidantsaddedafter4h.Fenretinidetreatmentisadded2hlaterandcellsareplatedinquadruplicatesin96wellplates(150μL/well).MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMalemice(C57Bl6)arefedastandardchoworahigh-fatdiet(HFD)from5to17weeks,atwhichpointhalf2/4www.MedChemEwww.MedChemEAdministration[2]oftheHFD-fedmicebeginreceivingfenretinideindrinkingwaterfor4weeks.Fenretinideisdissolvedin100%ethanolanddilutedinwaterto10μg/mL.Controltreatmentwaterreceivesanequalamountofethanol(0.5%).FENwaterispreparedinlow-lightconditionsandadministeredinlight-protectivebottles.Waterisreplacedevery1-2days,andnoprecipitationofFENisnotedatanytime.Animalweightsarerecordedatthebeginningandendofthetreatmentperiod.Followinga4-weekFENtreatment,miceundergointraperitonealglucoseandinsulintolerancetests.Forbothtests,micearefastedfor6handreceiveaninjectionofeitherglucose(1g/kgofbodyweight)orinsulin(0.75units/kgofbodyweight).BloodglucoseisdeterminedatthetimesindicatedbytheBayerContour®glucosemeter,andinsulinismeasuredwiththerat/mouseinsulinELISAkit.Theinsulinresistanceindexisassessedbyusingfastingbloodglucoseandinsulinlevelstocomputethehomeostaticmodelassessmentofinsulinresistance(HOMA-IR),whereahighernumberrepresentsgreaterinsulinresistance.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•BiomedPharmacother.2020May;125:109680.•JCancer.2019Nov1;10(27):6767-6778.•OncolRep.2018Jul;40(1):518-526.•Cornea.2018Dec;37(12):1579-1585.•Patent.20200038327A1.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Apraiz,Aintzane.,etal.Dihydroceramideaccumulationandreactiveoxygenspeciesaredistinctandnonessentialeventsin4-HPR-mediatedleukemiacelldeath.BiochemistryandCellBiology(2012),90(2),209-223.[2].Bikman,BenjaminT.,etal.FenretinidePreventsLipid-inducedInsulinResistancebyBlockingCeramideBiosynthesis.JournalofBiologicalChemistry(2012),287(21),17426-17437.[3].CooperJP