A939572-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEA939572Cat.No.:HY-50709CASNo.:1032229-33-6分?式:C??H??ClN?O?分?量:387.86作?靶點(diǎn):Stearoyl-CoADesaturase(SCD)作?通路:MetabolicEnzyme/Protease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:100mg/mL(257.82mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto60°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.5782mL12.8912mL25.7825mL5mM0.5156mL2.5782mL5.1565mL10mM0.2578mL1.2891mL2.5782mL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(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%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemESolubility:≥2.5mg/mL(6.45mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(6.45mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(6.45mM);ClearsolutionBIOLOGICALACTIVITY?物活性A939572?種有效的，具有?服活性的硬脂酰CoA去飽和酶1SCD1抑制劑，作?于mSCD1和hSCD1，IC50分別為<4nM和37nM。IC50&TargetIC50:[1]體外研究A939572exhibitsrobustinvivoactivitywithdose-dependentdesaturationindexloweringeffects[1].A939572isasmallmoleculethatspecificallyinhibitsSCD1enzymaticactivity.A939572demonstratesasignificantdose-dependentdecreaseinproliferationinCaki1,A498,Caki2,andACHNatday5(IC50sof65nM,50nM,65nM,and6nM,respectively).InA939572(SCDi)treatedCaki1andA498cells,allfiveERstressrelatedgenesareexpressedatsignificantlyincreasedlevelscomparedtoDMSO+BSAcontrol,andthiselevatedexpressioncanbeblockedwiththeadditionofOA-BSA[2].體內(nèi)研究Athymicnude(nu/nu)micebearingA498ccRCCxenograftsaretreatedwithA939572(30mg/kg,p.o.)andTemindividuallyorincombinationoverthecourseoffourweeks,andtumorvolume(mm3)isrecorded.A939572andTemmonotherapygeneratesimilargrowthresponseswithapproximately20-30%reductionsintumorvolume(vs.placebocontrol)beingobserveduponstudycompletion,withvaluesreachingstatisticalsignificanceonlywithinthelastweekoftreatment.Thecombinationgroupyieldsovera60%decreaseintumorvolume(vs.placebocontrol)bystudycompletionwithsignificantreductionsrecordedafterapproximately1weekoftreatment[2].PROTOCOLCellAssay[2]Cellsareplated(0.5or1×105/well)in24-wellplatesintriplicate.CellsarecountedusingaCoulterParticleCounter.Oleicacid-albuminisaddedtomediaat5μMol.A939572stocksarepreparedinDMSO.Temsirolimusdosingisperformed.Softagarculturesarepreparedbydiluting2×growthmedium1:1in1.5%Seaplaque?GTG?agarose,with500cells/platein60mmculturedishes.ColoniesarestainedwithGiemsaandcountedafter3wks[2].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[2]Administration[2]A498cellsaresubcutaneouslyimplantedinathymicnu/numiceat1×106cells/mousein50%Matrigel.Tumorsreach~50mm3priorto4wktreatment.A939572isre-suspendedinstrawberryflavoredKool-Aid?insterilizedH2O(0.2g/mL)vehicleat30mg/kgina50μLdose.Miceareorallyfedbyusingasyringetoadministerthe50μLdosetwicedaily/mouse.Thismodifiedmethodisfoundtobeeffectiveandlessstressful2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEonthemice.Temsirolimusissolubilizedin30%ethanol/salineandadministeredviaintraperitonealinjectionat10mg/kgina50μLdoseonceevery72hrs/mouse.Tumorvolumesarecalculatedusingtheformula0.5236(L*W*H)andbodyweightaremeasuredevery3days.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?JExpMed.2020Oct5;217(10):e20200318.?IntJBiolSci.2022;18(16):6114-6128.?SciChinaLifeSci.2021May27;1-21.?CellRep.2020Dec1;33(9):108444.?BrJCancer.2020Jun;122(12):1837-1847.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].XinZ,etal.Discoveryofpiperidine-arylurea-basedstearoyl-CoAdesaturase1inhibitors.BioorgMedChemLett.2008Aug1;18(15):4298-302.[2].vonRoemelingCA,etal.Stearoyl-CoAdesaturase1isanovelmoleculartherapeutictargetforclearcellrenalcellcarcinoma.ClinCancerRes.201