Aplaviroc-hydrochloride-AK602-hydrochloride-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEAplavirochydrochlorideCat.No.:HY-17450ACASNo.:461023-63-2Synonyms:AK602hydrochloride;GSK-873140hydrochloride;GW-873140hydrochloride分?式:C??H??ClN?O?分?量:614.17作?靶點:CCR;HIV作?通路:GPCR/GProtein;Immunology/Inflammation;Anti-infection儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:200mg/mL(325.64mM;Needultrasonic)MassSolvent1mg5mg10mgConcentration制備儲備液1mM1.6282mL8.1411mL16.2821mL5mM0.3256mL1.6282mL3.2564mL10mM0.1628mL0.8141mL1.6282mL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。-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?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，適當保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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)1/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE1.請依序添加每種溶劑：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥12.5mg/mL(20.35mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥12.5mg/mL(20.35mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥12.5mg/mL(20.35mM);ClearsolutionBIOLOGICALACTIVITY?物活性Aplaviroc(AK602)hydrochloride，SDP的?個衍?物，CCR5的拮抗劑，其對HIV-1Ba-L，HIV-1JRFL和HIV-1MOKW的IC50值為0.1-0.4nM。IC50&TargetHIV-1Ba-LHIV-1JRFLHIV-1MOKWCCR50.4nM(IC50)0.1nM(IC50)0.2nM(IC50)體外研究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].體內(nèi)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?邊的抑制劑?師www.MedChemEAK602/ONO4128/GW873140,inanovelhumanperipheralbloodmononuclearcellnonobesediabetic-SCID,interleukin-2receptorgamma-chain-knocked-outAIDSmousemodel.Virol.2005Feb;79(4):2087-96.McePdfHeightCaution:Producthasn