MLN-4760-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEMLN-4760Cat.No.:HY-19414CASNo.:305335-31-3分?式:C??H??Cl?N?O?分?量:428.31作?靶點(diǎn):Angiotensin-convertingEnzyme(ACE)作?通路:MetabolicEnzyme/Protease儲(chǔ)存?式:4°C,storedundernitrogen,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(storedunder

nitrogen,awayfrommoisture)溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥50mg/mL(116.74mM)H2O:<0.1mg/mL(ultrasonic;warming;adjustpHto11withNaOH;heatto60°C)(insoluble)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.3348mL11.6738mL23.3476mL5mM0.4670mL2.3348mL4.6695mL10mM0.2335mL1.1674mL2.3348mL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(storedundernitrogen,awayfrommoisture)。-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%salineSolubility:≥2.5mg/mL(5.84mM);Clearsolution1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.5mg/mL(5.84mM);Clearsolution3.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.5mg/mL(5.84mM);ClearsolutionBIOLOGICALACTIVITY?物活性MLN-4760?種有效、選擇性的?ACE2抑制劑，IC50值為0.44nM，對(duì)其選擇性對(duì)其他相關(guān)蛋?的5000多倍，包括?丸ACE(IC50，>100μM)和?carboxypeptidaseA(IC50，27μM)。IC50&TargetIC50:0.44nM(HumanACE2),27μM(BovinecarboxypeptidaseA)[1]體外研究MLN-4760isapotentandselectivehumanACE2inhibitor(IC50,0.44nM),withexcellentselectivity(>5000-fold)versusrelatedenzymeshumantesticularACE(IC50,>100μM)andbovinecarboxypeptidaseA(CPDA;IC50,27μM)[1].MLN-4760effectivelyquenchescleavageofthe7-Mca-YVADAPK(Dnp)inrhACE2.MLN-4760showspIC50atrhACE2of8.5±0.1andatrhACEof4.4±0.2.MLN-4760alsoshowspIC50atrhACE2of4.7±0.1,6.9±0.1andatACEof4.4±0.1,6.2±0.1inmurineheartandmononuclearcells(MNCs),resepctively[2].體內(nèi)研究MLN-4760(100μM,intracerebroventricularinfusionforfivedays)significantlyworsensneurologicalfunctionat4hand3dpost-strokewithoutsignificantlyincreasinginfarctvolume[3].PROTOCOLAnimalRats[3]Administration[3]InarelatedexperimenttoevaluatetheroleofcentralACE2instroke,randomlyassignedrats(n=16)aretreatedcentrallyforfivedayspriortoandthreedaysafterstrokewiththeACE2inhibitorMLN-4760(100μMinfusedatarateof0.5μL/h)orsterilesaline(0.9%)viaintracerebroventricularinfusion.Followingendothelin-1MCAO,neurologicalfunctionisassessedat4h,1d,and3d,andbrainsareharvestedat3dpost-strokeforinfarctvolumeanalysisasabove[3].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶(hù)使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?ActaPharmSinB.2021Jan;11(1):222-236.?CellSignal.2022Jul23;110418.?Biomedicines.2021,9(12),1902.?InfectDisTher.2021Feb2;1-12.?PharmBiol.2022Dec;60(1):979-989.Seemorecustomervalidationsonwww.MedChemE2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEREFERENCES[1].DalesNA,etal.Substrate-baseddesignofthefirstclassofangiotensin-convertingenzyme-relatedcarboxypeptidase(ACE2)inhibitors.JAmChemSoc.2002Oct9;124(40):11852-3.[2].JoshiS,etal.Angiotensinconvertingenzymeversusangiotensinconvertingenzyme-2selectivityofMLN-4760andDX600inhumanandmurinebonemarrow-derivedcells.EurJPharmacol.2016Mar5;774:25-33.[3].BennionDM,etal.ActivationoftheNeuroprotectiveAngiotensin-ConvertingEnzyme2inRatIschemicStroke.Hypertension.2015Jul;66(1):141-8.McePdfHeightCautio