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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Daclatasvir(Synonyms: BMS-790052; EBP 883)/HY-10466/10mM*1mL in DMSO
商品详细Medchemexpress/Daclatasvir(Synonyms: BMS-790052; EBP 883)/HY-10466/10mM*1mL in DMSO
Medchemexpress/Daclatasvir(Synonyms: BMS-790052; EBP 883)/HY-10466/10mM*1mL in DMSO
Medchemexpress/Daclatasvir(Synonyms: BMS-790052; EBP 883)/HY-10466/10mM*1mL in DMSO
商品编号： HY-10466-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1620.00
美元价： 972.00
产地： 美国(厂家直采)
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产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
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商品介绍
DaclatasvirisapotentHCVNS5Aproteininhibitor,withmeanEC50valuesof50and9pMagainstgenotype1aand1breplicons,respectively.

CustomerValidation

  • •EMBORep.2016Jul;17(7):1013-28.
  • •PLoSPathog.2017May11;13(5):e1006374.
  • •IntJRADIatOncolBiolPhys.2016Nov15;96(4):867-876.
  • •JVirol.2014May;88(10):5578-94.
  • •FrontPharmacol.2016Dec21;7:490.
  • •IntJAntimicrobAgents.2015Oct;46(4):381-8.
  • •AntimicrobAgentsChemother.2015May;59(5):2496-507.
  • •AntimicrobAgentsChemother.2014Aug;58(8):4555-64.
  • •AntimicrobAgentsChemother.2014Jun;58(6):3327-34.
  • •AntimicrobAgentsChemother.2013Mar;57(3):1180-91.
  • •AntiviralRes.2017Oct;146:191-200.
  • •AntiviralRes.2017Oct23;148:5-14.
  • •PLoSOne.2016Jul21;11(7):e0159511.
  • •PLoSOne.2016Apr22;11(4):e0152036.
  • •PLoSOne.2015Aug11;10(8):e0134707.
  • •VirusRes.2017Mar18;235:37-48.
  • •TransplInfectDis.2017Nov7.
  • •HepatolCommun.2017;1(6).
  • •HepatolCommun.June6,2017.
  • •OpenVirolJ.2014Mar7;8:1-8.
Description

DaclatasvirisapotentHCVNS5Aproteininhibitor,withmeanEC50valuesof50and9pMagainstgenotype1aand1breplicons,respectively.

IC50&Target

EC50:9±4pM(HCVreplicongenotype1b,inCon1cells),50±13pM(HCVreplicongenotype1a,inH77cells)[1]

InVitro

Daclatasvir(BMS-790052)isasmallmoleculeinhibitoroftheHCVNS5Aproteinthatexhibitspicomolarhalf-maximumeffectiveconcentrations(EC50)towardsrepliconsexpressingabroadrangeofHCVgenotypesandtheJFH-1genotype2ainfectiousvirusincellculture.DaclatasvirisapotentinhibitoroftheJFH-1genotype2ainfectiousvirusthatreplicatesincellculture(EC50=28pM),anassayconsideredtobeamoreBIOLOGicallyrelevantinvitrocellculturesystem.Inaddition,DaclatasvirdisplayssimilarpotencyinHuh-7,HeLaandHEK293Tcells,demonstratingthatthefunction(s)ofNS5AinhibitedbyDaclatasviris(are)highlyconservedindifferentcellularenvironments[1].

InVivo

Inarandomized,double-blind,placebo-controlled,singleascending-dosestudy,Daclatasvir(BMS-790052)isadmiNISTeredatsixdoselevelstohealthy,non-HCV-infectedsubjectsoverarangeof1to200mgasanoralsolution.Daclatasvirissafeandwelltoleratedupto200mgwithnoclinicallyrelevantadverseeffects.Afteroraladministration,Daclatasvirisreadilyabsorbed,withdose-proportionalexposuresoverthestudieddoserange,andallsubjectshavedrugconcentrationsgreaterthantheprotein-binding-adjustedEC90forgenotypes1aand1b,asmeasuredintherepliconassay,atandbeyond24hpost-dose.(Theproteinbinding-adjustedEC90figuresarederivedfromananalysisoftheeffectoftheadditionofhumanserumonantiviralactivityinreplicons.Inthepresenceof40%humanserum,theEC90forDaclatasviris383pM(0.28ng/mL)forthegenotype1arepliconand49pM(0.04ng/mL)forthegenotyope1breplicon)[1].MiceineachgroupthatdevelopedpersistentHCVinfectionaredividedintotwotreatmentgroups.Onegroupreceive4weeksofAsunaprevir/Daclatasvirtreatmentandtheothergroupreceived4weeksofLedipasvir/GS-558093treatment.Asunaprevir/DaclatasvirtherapyandLedipasvir/GS-558093therapyrapidlydeceaseserumHCVRNAlevelstobelowthesensitivity,andtheyarenotdetectedaftercompletionofthetherapyexceptfortwomiceintheLedipasvir/GS-558093group[2].

ClinicalTrial
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References

  • [1].GaoM,etal.ChemicalgeneticsstrategyidentifiesanHCVNS5Ainhibitorwithapotentclinicaleffect.Nature.2010May6;465(7294):96-100.

    [2].KaiY,etal.EmergenceofhepatitisCvirusNS5AL31VplusY93HvariantupontreatmentfailureofdaclatasvirandasunaprevirisrelativelyresistanttoledipasvirandNS5BpolymerasenucleotideinhibitorGS-558093inhumanhepatocytechimericmice.JGa

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM1.3534mL6.7670mL13.5340mL
5mM0.2707mL1.3534mL2.7068mL
10mM0.1353mL0.6767mL1.3534mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

Daclatasvir(BMS-790052)isdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].

HCVgenotype1aand1brepliconcellsaremaintainedinmediacontainingDaclatasvirataconcentrationof5-to20-foldaboveEC50and0.5mg/mLG418.RepliconcellssimilarlytreatedwithDMSOaremaintainedascontrols.Afterapproximately4-5weekswhencellgrowthissimilartoDMSO-treatedcontrolcells,selectedcellsareexpandedforresistancetestingandanalysisbyPCRwithreversetranscription[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[2]

Daclatasvir(BMS-790052)isdissolvedinDMSOanddilutedwithsaline[2].

Mice[2]
Humanizedliverchimericmice,whosechimericrateoftheliverisestimatedasover40%,areinjectedintravenouslywith100µLofHCV-positivehumanserumsamples.Afterinoculation,theirbloodiscollectedfromanexternaljugularveinevery1-4weeks.TheHCVRNAlevelsaremeasuredbytheCOBASTaqManHCVtestin100-folddilutedserumwithalowermeasurementrangeof3.2logIU/mLserum.AfterserumlevelsofHCVRNAreachplateaulevels,miceareadministeredorallyonceadayfor4weekswithoneofthefollowing:40mg/kgofAsunaprevirplus30mg/kgofDaclatasvir,15mg/kgofLedipasvirplus50mg/kgofGS-558093and50mg/kgofGS-558093plus400mg/kgofTelaprevir.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].GaoM,etal.ChemicalgeneticsstrategyidentifiesanHCVNS5Ainhibitorwithapotentclinicaleffect.Nature.2010May6;465(7294):96-100.

    [2].KaiY,etal.EmergenceofhepatitisCvirusNS5AL31VplusY93HvariantupontreatmentfailureofdaclatasvirandasunaprevirisrelativelyresistanttoledipasvirandNS5BpolymerasenucleotideinhibitorGS-558093inhumanhepatocytechimericmice.JGa

MolecularWeight

738.88

Formula

C₄₀H₅₀N₈O₆

CASNo.

1009119-64-5

Storage
Powder-20°C3years
 4°C2years
Insolvent-80°C6months
 -20°C1month
Shipping

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:≥40mg/mL

*"<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

Purity:99.31%