SN-38-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?Agonists?ScreeningLibrarieswww.MedChemESN-38Cat.No.:HY-13704CASNo.:86639-52-3分?式:C??H??N?O?分?量:392.4作?靶點(diǎn):Topoisomerase;ADCCytotoxin;Autophagy作?通路:CellCycle/DNADamage;Antibody-drugConjugate/ADCRelated;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:25mg/mL(63.71mM;Needultrasonic)掃描?維碼，H2O:<0.1mg/mL(insoluble)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1mM2.5484mL12.7421mL25.4842mL5mM0.5097mL2.5484mL5.0968mL10mM0.2548mL1.2742mL2.5484mL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:2.08mg/mL(5.30mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(5.30mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.8mg/mL的澄DMSO儲(chǔ)備液加到400μLPEG300中，混合均勻；向上述1/3www.MedChemEwww.MedChemE2.體系中加?50μLTween-80，混合均勻；然后繼續(xù)加?450μL?理鹽?定容?1mL。請(qǐng)依序添加每種溶劑：10%DMSO90%(20%SBE-β-CDinsaline)Solubility:2.08mg/mL(5.30mM);Suspendedsolution;Needultrasonic此?案可獲得2.08mg/mL(5.30mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。以1mL?作液為例，取100μL20.8mg/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(6.37mM);Suspendedsolution;Needultrasonic此?案可獲得2.5mg/mL(6.37mM)的均勻懸濁液，懸濁液可?于?服和腹腔注射。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SN-38(NK012)拓?fù)洚悩?gòu)酶I抑制劑伊?替康的活性代謝產(chǎn)物。SN-38(NK012)抑制DNA合成和RNA合成的IC50分別為0.077和1.3μM。IC50&TargetTopoisomeraseICamptothecins體外研究TheIC50valuesforLoVo,HCT116,andHT29celllinesis20nM,50nM,130nM,respectively.InallthreeSN-38(NK012)resistantcelllinesTop1activityismaintainedinthepresenceofhighconcentrationsofSN-38[2].體內(nèi)研究SN-38(NK012),theactiveandtoxicmetaboliteoftheanticancerprodrugIrinotecan.At30minutesafteradministration,IrinotecanplasmaconcentrationsinSlco1a/1b(?/?)miceare1.9-foldhigherthaninthewild-typemice(1.89vs.1.01μM,respectively),whereasSN-38(NK012)plasmaconcentrationsofSlco1a/1b(?/?)miceare8-foldhighercomparewithwild-typemice(0.4μg/mLvs.0.05μg/mL,respectively).Overallplasmaexposure[AUC(5-240)]ofIrinotecanis1.7-foldhigherinOatp1a/1bknockoutmiceversuswild-typemice(209.8±6.7vs.120.9±4.4μM/min;P<0.01),and2.9-foldhigherforSN-38(50±2.9vs.12±2μM/min;P<0.001)[3].PROTOCOLCellAssay[2]InvitroSN-38(NK012)sensitivityisdeterminedusingtheMTTassay.Cellsareseededin96-wellplates,andarangeofSN-38(NK012)concentrationsisaddedthefollowingday.Following48hofdrugexposure,themediumisdiscardedandtheplatesareincubatedwithmediumcontainingMTT(0.5mg/mL)for3h.Acidified(0.02MHCl)sodiumdodecylsulphate(20%)isaddedtodissolvetheformedformazan.Opticaldensityat570nm(and670nmforbackground)ismeasured,andthecellviabilityiscalculatedinpercentcomparedtountreatedcells.ExperimentsarerepeatedthreetimesandthemeanIC50value±standarddeviationisdetermined.RelativeresistanceforeachresistantcelllineiscalculatedbydividingthemeanIC50valueoftheresistantcelllinebythemeanIC50valueofthecorrespondingparentalcellline[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[3]2/3www.MedChemEwww.MedChemEAdministration[3]Femalewild-type,Slco1a/1b(?/?)(Oatp1a/1bknockout),Slco1a/1b(?/?);1B1(tg),andSlco1a/1b(?/?);1B3(tg)(liver-specificOATP1B1andOATP1B3humanizedtransgenic)miceofcomparablegeneticbackground(>99%FVB)between8and14weeksofageareused.Irinotecan(20mg/mLinwater-basedsolutioncontainingNaOH,lacticacid,andsorbitol)isdilutedwithsaline(to2mg/mL)foradministrationof10mg/kg;5μL/gbodyweightareadministeredintravenouslytomice.SN-38(NK012)isdissolvedinDMSO(1mg/mL)and1μL/gbodyweightisadministeredintravenouslytomicetoachieveadosageof1mg/kg.Theexperimentsareterminatedbyisofluraneanaesthesia,heparin-bloodsamplingbycardiacpuncturefollowedbycervicaldislocationandtissuecollection.Bloodsamplesarecentrifugedat5,200×gfor5minutesat4°Candplasmaiscollectedandstoredat?30°Cuntilanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JControlRelease.2020Oct10;326:387-395.?CarbohydPolym.2020May1;235:115983.?IntJNanomedicine.2020Sep15;15:6839-6854.?INTJPHARMACEUT.2020May.?IntJPharm.2019Oct5;569:118588.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].WallinA,etal.AnticancereffectofSN-38oncoloncancercelllineswithdifferentmetastaticpotential.OncolRep.2008Jun;19(6):1493-8.[2].JensenNF,etal.CharacterizationofDNAtopoisomeraseIinthreeSN-38resistanthumancoloncancercelllinesrevealsanewpairofresistance-associatedmutations.JExpClinCancerRes.2016Mar31;35:56.[3].StewartCF,etal.DispositionofirinotecanandSN-38followingoralandintravenousirinotecandosinginmice.CancerChemotherPharmacol.1997;40(3):259-65.M