Raltegravir-potassium-MK-0518-potassium-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemERaltegravirpotassiumCat.No.:HY-10353ACASNo.:871038-72-1Synonyms:MK0518potassium分⼦式:C₂₀H₂₀FKN₆O₅分⼦量:482.51作⽤靶点:HIVIntegrase;HIV作⽤通路:MetabolicEnzyme/Protease;Anti-infection储存⽅式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性数据体外实验H2O:25mg/mL(51.81mM;Needultrasonic)DMSO:20.83mg/mL(43.17mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制备储备液1mM2.0725mL10.3625mL20.7250mL5mM0.4145mL2.0725mL4.1450mL10mM0.2072mL1.0362mL2.0725mL请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；⼀旦配成溶液，请分装保存，避免反复冻融造成的产品失效。储备液的保存⽅式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C储存时，请在6个⽉内使⽤，-20°C储存时，请在1个⽉内使⽤。体内实验请根据您的实验动物和给药⽅式选择适当的溶解⽅案。以下溶解⽅案都请先按照InVitro⽅式配制澄的储备液，再依次添加助溶剂：(为保证实验结果的可靠性，澄的储备液可以根据储存条件，适当保存；体内实验的⼯作液，建议您现⽤现配，当天使⽤；以下溶剂前显⽰的百分⽐指该溶剂在您配制终溶液中的体积占⽐；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的⽅式助溶)1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%saline1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemESolubility:≥2.08mg/mL(4.31mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.31mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.31mM);Clearsolution4.请依序添加每种溶剂：PBSSolubility:25mg/mL(51.81mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY⽣物活性Raltegravir(MK0518)potassium⼀种有效的integrase抑制剂，⽤于研究HIV感染。体外研究PFVINcarryingtheS217Hsubstitutionis10-foldlesssusceptibletoRaltegravirwithIC50of900nM.PFVINdisplays10%ofWTactivityandisinhibitedbyRaltegravirwithanIC50of200nM,indicatingaapprtwofolddecreaseinsusceptibilitytotheINstrandtransferinhibitor(INSTI)comparedwithWTIN.S217QPFVINisassensitivetoRaltegravirastheWTenzyme[1].Raltegravirismetabolizedbyglucuronidation,nothepatically.RaltegravirhaspotentinvitroactivityagainstHIV-1,witha95%inhibitoryconcentrationof31±20nM,inhumanTlymphoidcellcultures.RaltegravirisalsoactiveagainstHIV-2whenRaltegraviristestedinCEMx174cells,withanIC95of6nM.Raltegravirmetabolismoccursprimarilythroughglucuronidation.Drugsthatarestronginducersoftheglucuronidationenzyme,UGT1A1,significantlyreduceRaltegravirconcentrationsandshouldnotbeused.RaltegravirexhibitsweakinhibitoryeffectsonhepaticcytochromeP450activity.RaltegravirdoesnotinduceCYP3A4RNAexpressionorCYP3A4-dependenttestosterone6-β-hydroxylaseactivity[2].Raltegravircellularpermeativityisreducedinthepresenceofmagnesiumandcalcium[3].RaltegravirandrelatedHIV-1integrase(IN)strandtransferinhibitors(INSTIsefficientlyblockviralreplication[4].InacutelyinfectedhumanlymphoidCD4+T-celllinesMT-4andCEMx174,SIVmac251replicationisefficientlyinhibitedbyRaltegravir,whichshowsanEC90inthelownanomolarrange[5].体内研究Raltegravirinducesviro-immunologicalimprovementofnonhumanprimateswithprogressingSIVmac251infection.Onenon-humanprimateshowsanundetectableviralloadfollowingRaltegravirmonotherapy[5].PROTOCOLCellAssay[5]HumanMT-4cellsareinfectedfor2hourswiththeSIVmac251,HIV-1(IIIB)andHIV-2(CDC77618)stocksatamultiplicityofinfectionof,approximately,0.1.Cellsarethenwashedthreetimesinphosphatebufferedsaline,andsuspendedat5×105/mLinfreshculturemedium(toprimarycells50units/mLofIL-2areadded)in96-wellplates,inthepresenceorabsenceofarangeoftriplicateraltegravirconcentrations(0.0001μM-1μM).Untreatedinfectedandmock-infectedcontrolsarepreparedtoo,inordertoallowcomparisonofthedataderivedfromthedifferenttreatments.ViralcytopathogeniciyinMT-4cellsisquantitatedbythemethyltetrazolium(MTT)method(MT-4/MTTassay)whenextensivecelldeathincontrolvirus-infectedcellculturesisdetectablemicroscopicallyaslackofcapacitytore-cluster.ThecapabilityofMT-4cellstoformclustersafterinfection.Briefly,clustersaredisruptedbypipetting;and,after2hoursofincubationat37°C,theformationofnewclustersisassessedbylightmicroscopy(100×magnification).Cellculturesupernatantsare2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEcollectedforHIV-1p24andHIV-2/SIVmac251p27coreantigenmeasurementbyELISA.InCEMx174-infectedcellcultures,whichshowapropensitytoformsyncytiainducedbythevirusenvelopeglycoproteins,syncytiaarecounted,inblindedfashion,bylightmicroscopyforeachwellat5daysfollowinginfection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.户使⽤本产品发表的科研⽂献•JInfectDis.2022Sep19;jiac386.•LifeSci.9September2022,120948.•Phytomedicine.2016Nov15;23(12):1383-1391.•JVirol.2017Jan18;91(3).pii:e02152-16.•Viruses.2021Jan18;13(1):E131.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].Hare,S.,etal.,Molecularmechanismsofretroviralintegraseinhibitionandtheevolutionofviralresistance.ProcNatlAcadSciUSA,2010.107(46):p.20057-62.[2].HicksC,etal.Raltegravir:thefirstHIVtype1integraseinhibitor.ClinInfectDis.2009Apr1;48(7):931-9[3].MossDM,etal.DivalentmetalsandpHalterraltegravirdispositioninvitro.AntimicrobAgentsChemother.2012Jun;56(6):3020-6[4].HareS,etal.Structuralandfunctio