Fenretinide-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemEFenretinideCat.No.:HY-15373CASNo.:65646-68-6分?式:C??H??NO?分?量:391.55作?靶點(diǎn):RAR/RXR;Autophagy作?通路:MetabolicEnzyme/Protease;Autophagy儲(chǔ)存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥130mg/mL(332.01mM)掃描?維碼，*"≥"meanssoluble,butsaturationunknown.運(yùn)?溶解?案計(jì)算器獲得適合您實(shí)驗(yàn)體系的溶解?案MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5540mL12.7698mL25.5395mL5mM0.5108mL2.5540mL5.1079mL10mM0.2554mL1.2770mL2.5540mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存?式和期限。體內(nèi)實(shí)驗(yàn)請(qǐng)根據(jù)您的實(shí)驗(yàn)動(dòng)物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請(qǐng)先按照InVitro?式配制澄的儲(chǔ)備液，再依次添加助溶劑：為保證實(shí)驗(yàn)結(jié)果的可靠性，澄的儲(chǔ)備液可以根據(jù)儲(chǔ)存條件，適當(dāng)保存；體內(nèi)實(shí)驗(yàn)的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)天使?；以下溶劑前顯?的百分?指該溶劑在您配制終溶液中的體積占?；如在配制過(guò)程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過(guò)加熱和/或超聲的?式助溶1.請(qǐng)依序添加每種溶劑：10%DMSO40%PEG3005%Tween-8045%salineSolubility:≥2.5mg/mL(6.38mM);Clearsolution此?案可獲得≥2.5mg/mL(6.38mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。1/4www.MedChemEwww.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.38mM);Clearsolution此?案可獲得≥2.5mg/mL(6.38mM，飽和度未知)的澄溶液。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL20%的SBE-β-CD?理鹽??溶3.液中，混合均勻。請(qǐng)依序添加每種溶劑：10%DMSO90%cornoilSolubility:≥2.5mg/mL(6.38mM);Clearsolution此?案可獲得≥2.5mg/mL(6.38mM，飽和度未知)的澄溶液，此?案不適?于實(shí)驗(yàn)周期在半個(gè)?以上的實(shí)驗(yàn)。以1mL?作液為例，取100μL25.0mg/mL的澄DMSO儲(chǔ)備液加到900μL??油中，混合均勻。BIOLOGICALACTIVITY?物活性Fenretinide(4-HPR)?種合成的類維?素A衍?物，能夠結(jié)合視酸受體(RAR)誘導(dǎo)細(xì)胞死亡。體外研究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].體內(nèi)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.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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