Aplaviroc-hydrochloride-AK602-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

Hotline:400-820-3792Inhibitors•ScreeningLibraries•Proteinswww.MedChemEAplavirochydrochlorideCat.No.:HY-17450ACASNo.:461023-63-2Synonyms:AK602hydrochloride;GSK-873140hydrochloride;GW-873140hydrochloride分⼦式:C₃₃H₄₄ClN₃O₆分⼦量:614.17作⽤靶点:CCR;HIV作⽤通路:GPCR/GProtein;Immunology/Inflammation;Anti-infection储存⽅式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性数据体外实验DMSO:200mg/mL(325.64mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制备储备液1mM1.6282mL8.1411mL16.2821mL5mM0.3256mL1.6282mL3.2564mL10mM0.1628mL0.8141mL1.6282mL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)1/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemE1.请依序添加每种溶剂：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥12.5mg/mL(20.35mM);Clearsolution2.请依序添加每种溶剂：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥12.5mg/mL(20.35mM);Clearsolution3.请依序添加每种溶剂：10%DMSO>>90%cornoilSolubility:≥12.5mg/mL(20.35mM);ClearsolutionBIOLOGICALACTIVITY⽣物活性Aplaviroc(AK602)hydrochloride，SDP的⼀个衍⽣物，CCR5的拮抗剂，其对HIV-1Ba-L，HIV-1JRFL和HIV-1MOKW的IC50值为0.1-0.4nM。IC50&TargetHIV-1Ba-LHIV-1JRFLHIV-1MOKWCCR50.4nM(IC50)0.1nM(IC50)0.2nM(IC50)体外研究Aplavirocexertspotentactivityagainstthreewild-typeR5HIV-1strains(HIV-1Ba-L,HIV-1JRFLandHIV-1MOKW)withIC50valuesof0.1to0.4nM.AplavirocissubstantiallymorepotentthantwopreviouslypublishedCCR5inhibitors,E921/TAK-779andAK671/SCH-C.AplavirocsuppressestheinfectivityandreplicationoftwoHIV-1MDRvariants,HIV-1MMandHIV-1JSL,atextremelylowconcentrations(IC50valuesof0.4to0.6nM).AplavirocbindstoCCR5withhighaffinity.TheKdvaluesthusdeterminedforAplaviroc,E913,E921/TAK-779,andAK671/SCH-Care2.9±1.0,111.7±3.5,32.2±9.6,and16.0±1.5nM,respectively.Aplavirocpotentlyblocksrgp120/sCD4bindingtoCCR5withanIC50valueof2.7nM.TheseresultssuggestthatthepotentactivityofAplavirocagainstR5HIV-1stemsfromitsbindingtoECL2Band/oritsvicinitywithhighaffinity,resultingininhibitionofgp120/CD4bindingtoCCR5[1].体内研究TheconcentrationofAplaviroc(AK602)reachedthemaximalconcentrationimmediatelyafterintraperitonealadministrationanddecreasedrapidly[2].Aplaviroc(AK602,60mg/kg,bid,daily)suppressesR5HIV-1viremiainhu-PBMC-NOGmice[2].AnimalModel:hu-PBMC-NOGmice[2].Dosage:60mg/kg.Administration:Singleintraperitonealadministration,bid,daily.Result:ThenumbersofCD4+cells/μLinsaline-treatedmiceweresignificantlylessthanthoseofAK602-treated,ddI-treated,oruninfectedmice.REFERENCES[1].MaedaK,etal.Spirodiketopiperazine-basedCCR5inhibitorwhichpreservesCC-chemokine/CCR5interactionsandexertspotentactivityagainstR5humanimmunodeficiencyvirustype1invitro.JVirol.2004Aug;78(16):8654-62.[2].HirotomoNakata,etal.Potentanti-R5humanimmunodeficiencyvirustype1effectsofaCCR5antagonist,2/3MasterofBioactiveMolecules—您⾝边的抑制剂⼤师www.MedChemEAK602/ONO4128/GW873140,inanovelhumanperipheralbloodmononuclearcellnonobesediabetic-SCID,interleukin-2receptorgamma-chain-knocked-outAIDSmousemodel.Virol.2005Feb;79(4):2087-96.McePdfHeightCaution:Producthasn