Obefazimod-ABX464-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEObefazimodCat.No.:HY-100870CASNo.:1258453-75-6Synonyms:ABX464分⼦式:C₁₆H₁₀ClF₃N₂O分⼦量:338.71作⽤靶点:HIV作⽤通路:Anti-infection储存⽅式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:≥100mg/mL(295.24mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制备储备液1mM2.9524mL14.7619mL29.5238mL5mM0.5905mL2.9524mL5.9048mL10mM0.2952mL1.4762mL2.9524mL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。-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:≥3.75mg/mL(11.07mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥3.75mg/mL(11.07mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Obefazimod(ABX464)⼀种有效的抗HIV剂。Obefazimod作⽤于受刺激的外周⾎单个核细胞(PBMCs)，抑制HIV-1复制，IC50为0.1μM⾄0.5μM。IC50&TargetHIV-10.1-0.5μM(IC50,inPBMCs)体外研究ObefazimodinhibitsHIV-1productioninPBMC-andmacrophages-infectedcells.ObefazimodhasastronginhibitoryeffectforallHIV-1subtypestestedincludingsubtypeB,Candrecombinantviruses.Obefazimodalsoveryefficientlyinhibitsthereplicationofviralstrainsharbouringmutationsthatconferresistancetodifferenttherapeuticagentsinvitro.Whiletheantiviraldrug3TCisnothighlyactiveonK65RandM184Vmutantstrains,bothstrainsareinhibitedbyObefazimod.TogeneralizetheeffectofObefazimodonHIV-1replicationinotherprimarycells,cellsaretreatedwithbetween0.01μMupto30μMconcentrationsofObefazimodandp24antigenlevelsaremonitoredinculturesupernatantsovera12daysperiod.Obefazimodefficientlyblocksvirusreplicationinadose-dependentmannerwithanIC50rangingbetween0.1μMand1μM[1].体内研究Humanizedmicereconstitutedwithhumanlymphoidcellsproviderapid,reliable,reproducibleexperimentalsystemsfortestingtheefficacyofObefazimodinvivo.Intheinitialsetting,SCIDmicearereconstitutedwithPBMCsandtheninfectedwiththeHIV-1strainJR-CSF.Micearetreatedtwiceaday(b.i.d)for15daysbyoralgavagewith20mg/kgofObefazimod.MeasuresofviralRNAshowthattheoraltreatmentwithObefazimodisabletosignificantlyreducetheviralloadoveraperiodof15daysoftreatment.FACSanalysisofbloodsamplesshowthattreatmentwithObefazimodpreventsdepletionofCD4+cellsfollowinginfectionofreconstitutedmiceandtherebyrestorestheCD8+/CD4+ratiobacktothatofnon-infectedmice[1].PROTOCOLCellAssay[1]TheconcentrationofABX464withminimalsideeffectsoncellviabilityisdeterminedusinganMTStest.PBMCsaretreatedwithABX464(2,4,8,16,31,63,125,and250μM).CellviabilityismeasuredbyMTSassayafter6daysofincubationandcytotoxicityisindicatedaspercentageascomparedwithuntreatedcells[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalMice[1]Administration[1]SCIDmicearereconstitutedwithfreshhumanPBMCsfortwoweeksandthereconstitutionratesareestimatedbyhumanIgGtitration.ReconstitutedSCIDmiceareinfectedwithJRCSFHIV-1strainbyintraperitonealinjection.Controlgroupreceivelabrafiland5%DMSObygavage(n=15)andthetreated2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEgroupreceive20mg/kgb.i.dofABX464(n=14)for15days[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].CamposN,etal.LonglastingcontrolofviralreboundwithanewdrugABX464targetingRev-mediatedviralRNAbiogenesis.Retrovirology.2015Apr9;12:30.McePdfHeig