Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEML385Cat.No.:HY-100523CASNo.:846557-71-9分?式:C??H??N?O?S分?量:511.59作?靶點(diǎn):Keap1-Nrf2;Ferroptosis作?通路:NF-κB;Apoptosis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:33.33mg/mL(65.15mM;ultrasonicandwarmingandheatto60°C)H2O:<0.1mg/mL(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM1.9547mL9.7735mL19.5469mL5mM0.3909mL1.9547mL3.9094mL10mM0.1955mL0.9773mL1.9547mL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；?旦配成溶液，請(qǐng)分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲(chǔ)備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?，-20°C儲(chǔ)存時(shí)，請(qǐng)?jiān)?個(gè)?內(nèi)使?。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?；如在配制過程中出現(xiàn)沉淀、析出現(xiàn)象，可以通過加熱和/或超聲的?式助溶)1.請(qǐng)依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.08mg/mL(4.07mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(4.89mM);Clearsolution3.請(qǐng)依序添加每種溶劑：15%SolutolHS15>>10%CremophorEL>>35%PEG400>>40%waterSolubility:5mg/mL(9.77mM);Suspendedsolution;Needultrasonic4.請(qǐng)依序添加每種溶劑：50%PEG300>>50%salineSolubility:10mg/mL(19.55mM);Suspendedsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性ML385特異的NRF2抑制劑，IC50為1.9μM。IC50&TargetIC50:1.9μM(NRF2)[1]體外研究ML385interactswithNRF2andaffectstheDNAbindingactivityoftheNRF2-MAFGproteincomplex.TheadditionofML385decreasesanisotropyinadose-dependentmanner,withanIC50of1.9μM.Adose-dependentreductionintheNRF2transcriptionalactivityisobservedandthemaximuminhibitoryconcentrationis5μMbyML385.TreatmentwithML385leadstoasignificantreductioninNRF2anddownstreamtargetgeneexpressionselectivelyinKEAP1mutantH460cells.ML385selectivelyaffectsthecolonyformingabilityorgrowthoflungcancercellswithgainofNRF2function[1].體內(nèi)研究ML385incombinationwithcarboplatinleadstoasignificantreductionintumorcellproliferation,demonstratedbyfewerKi-67positivecells.TumorsamplestreatedwithML385showasignificantreductioninNRF2proteinlevelanditsdownstreamtargetgenes[1].ML385(intraperitonealinjection;30mg/kg;7days)weakensthetherapeuticeffectsofMSC-Exooninflammation-inducedastrocyticactivationinmice,andreducesreactiveastrogliosis,NF-κBdeactivation[3].AnimalModel:8-week-oldC57B/6malemice[3]Dosage:30mg/kg;7daysAdministration:IntraperitonealinjectionResult:ReversedinhibitionofMSC-Exoonhippocampalastrocyticactivationinvivo.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?Nature.2022Oct;610(7931):366-372.?CancerCell.2021May10;39(5):678-693.e11.?NatCommun.2018Oct24;9(1):4429.?Biomaterials.2020Oct;257:120264.?ActaPharmSinB.2021May;11(5):1246-1260.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESeemorecustomervalidationsonwww.MedChemEREFERENCES[1].SinghA,etal.SmallMoleculeInhibitorofNRF2SelectivelyIntervenesTherapeuticResistanceinKEAP1-DeficientNSCLCTumors.ACSChemBiol.2016Nov18;11(11):3214-3225.[2].XinnongLiu,etal.IsoliquiritigeninamelioratesacutepancreatitisinmiceviainhibitionofoxidativestressandmodulationoftheNrf2/HO-1pathway.OxidMedCellLongev.20March2018.[3].XianP,etal.Mesenchymalstemcell-derivedexosomesasananotherapeuticagentforameliorationofinflammation-inducedastrocytealterationsinmice.Theranostics.2019Aug14;9(20):5956-5975.McePdfHeightCaution:Product