雷特格韦钾盐 Raltegravir potassium 871038-72-1

雷特格韦钾盐 Raltegravir potassium 871038-72-1

生物活性

Raltegravir Potassium是一种具有口服活性的raltegravir钾盐。Raltegravir是HIV-1 integrase抑制剂。

体外研究

PFVINcarryingtheS217Hsubstitutionis10-foldlesssusceptibletoRaltegravirwithIC50of900nM.PFVINdisplays10%ofWTactivityandisinhibitedbyRaltegravirwithanIC50of200nM,indicatingaapprtwofolddecreaseinsusceptibilitytotheINstrandtransferinhibitor(INSTI)comparedwithWTIN.S217QPFVINisassensitivetoRaltegravirastheWTenzyme.Raltegravirismetabolizedbyglucuronidation,nothepatically.RaltegravirhaspotentinvitroactivityagainstHIV-1,witha95%inhibitoryconcentrationof31±20nM,inhumanTlymphoidcellcultures.RaltegravirisalsoactiveagainstHIV-2whenRaltegraviristestedinCEMx174cells,withanIC95of6nM.Raltegravirmetabolismoccursprimarilythroughglucuronidation.Drugsthatarestronginducersoftheglucuronidationenzyme,UGT1A1,significantlyreduceRaltegravirconcentrationsandshouldnotbeused.RaltegravirexhibitsweakinhibitoryeffectsonhepaticcytochromeP450activity.RaltegravirdoesnotinduceCYP3A4RNAexpressionorCYP3A4-dependenttestosterone6-β-hydroxylaseactivity.Raltegravircellularpermeativityisreducedinthepresenceofmagnesiumandcalcium.RaltegravirandrelatedHIV-1integrase(IN)strandtransferinhibitors(INSTIsefficientlyblockviralreplication.InacutelyinfectedhumanlymphoidCD4+T-celllinesMT-4andCEMx174,SIVmac251replicationisefficientlyinhibitedbyRaltegravir,whichshowsanEC90inthelownanomolarrange.

体内研究

Raltegravirinducesviro-immunologicalimprovementofnonhumanprimateswithprogressingSIVmac251infection.Onenon-humanprimateshowsanundetectableviralloadfollowingRaltegravirmonotherapy.