Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemERaltegravirpotassiumCat.No.:HY-10353ACASNo.:871038-72-1Synonyms:MK0518potassium分?式:C??H??FKN?O?分?量:482.51作?靶點:HIVIntegrase;HIV作?通路:MetabolicEnzyme/Protease;Anti-infection儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗H2O:25mg/mL(51.81mM;Needultrasonic)DMSO:20.83mg/mL(43.17mM;ultrasonicandwarmingandheatto60°C)MassSolvent1mg5mg10mgConcentration制備儲備液1mM2.0725mL10.3625mL20.7250mL5mM0.4145mL2.0725mL4.1450mL10mM0.2072mL1.0362mL2.0725mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度選擇合適的溶劑配制儲備液；?旦配成溶液，請分裝保存，避免反復(fù)凍融造成的產(chǎn)品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month(sealedstorage,awayfrommoisture)。-80°C儲存時，請在6個?內(nèi)使?，-20°C儲存時，請在1個?內(nèi)使?。體內(nèi)實驗請根據(jù)您的實驗動物和給藥?式選擇適當(dāng)?shù)娜芙?案。以下溶解?案都請先按照InVitro?式配制澄的儲備液，再依次添加助溶劑：(為保證實驗結(jié)果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當(dāng)保存；體內(nèi)實驗的?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(4.31mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(4.31mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(4.31mM);Clearsolution4.請依序添加每種溶劑：PBSSolubility:25mg/mL(51.81mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Raltegravir(MK0518)potassium?種有效的integrase抑制劑，?于研究HIV感染。體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEcollectedforHIV-1p24andHIV-2/SIVmac251p27coreantigenmeasurementbyELISA.InCEMx174-infectedcellcultures,whichshowapropensitytoformsyncytiainducedbythevirusenvelopeglycoproteins,syncytiaarecounted,inblindedfashion,bylightmicroscopyforeachwellat5daysfollowinginfection.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?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