Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEObefazimodCat.No.:HY-100870CASNo.:1258453-75-6Synonyms:ABX464分?式:C??H??ClF?N?O分?量:338.71作?靶點(diǎn):HIV作?通路:Anti-infection儲(chǔ)存?式:Powder-20°C3yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實(shí)驗(yàn)DMSO:≥100mg/mL(295.24mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲(chǔ)備液1mM2.9524mL14.7619mL29.5238mL5mM0.5905mL2.9524mL5.9048mL10mM0.2952mL1.4762mL2.9524mL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。-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(qǐng)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:≥3.75mg/mL(11.07mM);Clearsolution2.請(qǐng)依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥3.75mg/mL(11.07mM);ClearsolutionBIOLOGICALACTIVITY?物活性O(shè)befazimod(ABX464)?種有效的抗HIV劑。Obefazimod作?于受刺激的外周?單個(gè)核細(xì)胞(PBMCs)，抑制HIV-1復(fù)制，IC50為0.1μM?0.5μM。IC50&TargetHIV-10.1-0.5μM(IC50,inPBMCs)體外研究ObefazimodinhibitsHIV-1productioninPBMC-andmacrophages-infectedcells.ObefazimodhasastronginhibitoryeffectforallHIV-1subtypestestedincludingsubtypeB,Candrecombinantviruses.Obefazimodalsoveryefficientlyinhibitsthereplicationofviralstrainsharbouringmutationsthatconferresistancetodifferenttherapeuticagentsinvitro.Whiletheantiviraldrug3TCisnothighlyactiveonK65RandM184Vmutantstrains,bothstrainsareinhibitedbyObefazimod.TogeneralizetheeffectofObefazimodonHIV-1replicationinotherprimarycells,cellsaretreatedwithbetween0.01μMupto30μMconcentrationsofObefazimodandp24antigenlevelsaremonitoredinculturesupernatantsovera12daysperiod.Obefazimodefficientlyblocksvirusreplicationinadose-dependentmannerwithanIC50rangingbetween0.1μMand1μM[1].體內(nèi)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?邊的抑制劑?師www.MedChemEgroupreceive20mg/kgb.i.dofABX464(n=14)for15days[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.REFERENCES[1].CamposN,etal.LonglastingcontrolofviralreboundwithanewdrugABX464targetingRev-mediatedviralRNAbiogenesis.Retrovirology.2015Apr9;12:30.McePdfHeig