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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Dolutegravir（同义词：S/GSK1349572；GSK1349572）/HY-13238/1g
商品详细Medchemexpress/Dolutegravir（同义词：S/GSK1349572；GSK1349572）/HY-13238/1g
Medchemexpress/Dolutegravir（同义词：S/GSK1349572；GSK1349572）/HY-13238/1g
Medchemexpress/Dolutegravir（同义词：S/GSK1349572；GSK1349572）/HY-13238/1g
商品编号： HY-13238-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1760.00
美元价： 1056.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
联系Q Q： 3392242852
电话号码： 4000-520-616
电子邮箱： info@ebiomall.com
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商品介绍
DolutegravirisaninhibitorofHIV-1integrase-catalyzedstrandtransferwithIC50of2.7nM.

CustomerValidation

  • •CellPhysiolBiochem.2016Jul21;39(2):639-650.
  • •BiochemBiophysResCommun.2017Jul1;488(3):433-438.
Description

DolutegravirisaninhibitorofHIV-1integrase-catalyzedstrandtransferwithIC50of2.7nM.

IC50&Target

IC50:2.7nM(HIV-1integrase)[1]

InVitro

TheEC50ofDolutegravir(S/GSK1349572)againstHIV-1is0.51nMinPBMCs,0.71nMinMT-4cells,and2.2nMinthePHIVassay,whichusesapseudotypedself-inactivatingvirus.The50%cytotoxicconcentrations(CC50)forDolutegravirinproliferatingIM-9,U-937,MT-4,andMolt-4cellsare4.8,7.0,14,and15μM,respectively.InunstimulatedandstimulatedPBMCs,theCC50are189μMand52μM,respectively.BasedontheEC50ofDolutegraviragainstHIV-1inPBMCs(i.e.,0.51nM),thistranslatestoacell-basedtherapeuticindexofatleast9,400[1].

InVivo

Followingasingleintravenous(IV)admiNISTrationofDolutegravir,theplasmaclearanceislowinrats(0.23mL/min/kg)andmonkeys(2.12mL/min/kg).Thehalf-livesintheratandmonkeyaresimilar,approximately6h,andthesteady-statevolumeofdistribution(VSS)islow.Followingoraladministration,DolutegravirisrapidlyabsorbedwithahighoralbioavailABIlitywhenadministeredasasolutiontofastedmaleratsandasinglemonkey(75.6and87.0%,respectively).Dolutegravirexposure(CmaxandAUC)increasedwithincreasingdosefollowingoraladministrationofasUSPensiontonon-fastedratsupto250mg/kgandnon-fastedmonkeysupto50mg/kg,althoughtheincreaseislessthanproportional[2].

ClinicalTrial
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References

  • [1].KobayashiM,etal.InVitroantiretroviralpropertiesofS/GSK1349572,anext-generationHIVintegraseinhibitor.AntimicrobAgentsChemother.2011Feb;55(2):813-21.

    [2].MossL,etal.Thecomparativedispositionandmetabolismofdolutegravir,apotentHIV-1integraseinhibitor,inmice,rats,andmonkeys.Xenobiotica.2015Jan;45(1):60-70.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.3845mL11.9224mL23.8447mL
5mM0.4769mL2.3845mL4.7689mL
10mM0.2384mL1.1922mL2.3845mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
CellAssay
[1]

Dolutegravir(S/GSK1349572)isdissolvedinstocksolutions,andthendilutedwithappropriatemediabeforeuse[1].

Invitrogrowthinhibition(cytotoxicity)studiesareconductedwithS/GSK1349572(0.16,0.8,4,and20nM)inproliferatinghumanleukemicandlymphomiccelllines(IM-9,U-937,MT-4,andMolt-4)aswellasinstimulatedandunstimulatedhumanPBMCs.ATPlevelsarequantifiedbyusingtheCellTiter-Gloluciferasereagenttomeasuretheabilityofacompoundtoinhibitcellgrowthasanindicatorofthecompound"spotentialforcytotoxicity[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[2]

Dolutegravir(S/GSK1349572)isformulatedasasolutioninN,N-dimethylacetamideanddilutedwith50mMN-methylglucaminein3%mannitol(intravenous)[2].
Dolutegravir(S/GSK1349572)isformulatedasasolutioninD:Solutol:50mMN-methylglucaminein3%mannitol(1:1:8,v:w:v)(orallyadministeredtofastedratsandmonkeys)[2].
Dolutegravir(S/GSK1349572)isformulatedasasuspensionin0.5%hydroxypropylmethylcellulose(HPMC)/0.1%polyoxyethylenesorbitanmonooleate(Tween80)(orallyadministeredtonon-fastedratsandmonkeys)[2].

ForratandmonkeyPKstudies,Dolutegravirisadministeredasthefreeacidorthesodiumsalt.Alldosesarepresentedintermsofthefreeacid.Dolutegravirisadministeredbyintravenous(IV)short-term(within2min)bolus(1mg/kg)tothreemaleratsandtwomalemonkeys.Forsingleoraladministration,Dolutegravirasasolution(5mg/kg)isadministeredtothreefastedmaleratsandtwofastedmalemonkeys.Dolutegravirisadministeredassingleoraldosesof5,50,100,and250mg/kgtonon-fastedmalerats(n=2/doselevel)and3,10,and50mg/kgtonon-fastedfemalemonkeys.Forintravenousadministration,bloodsamplesarecollectedfromrats(0.2mLviajugularveincannula)andmonkeys(approximately0.2or0.5mLviasaphenousveininahindlimb)intoNa2EDTA-treatedsyringesat0.083,0.25,0.5,1,2,4,6,8,and24h.Fororaladministration,samplesarecollectedat0.25(ratsonly),0.5,1,2,4,6[rats(solutionandsuspension)andmonkey(solutiononly)],8,and24h.Followingcollection,thebloodisimmediatelyputonweticeandthencentrifugedwithinanhourat1740gfor10minat4°Ctoobtainplasma.Allsamplesarestoredatapproximately-20°CorcolderpriortoanalysisbyusingamethodbasedonproteinprecipitationandLC-MS/MSanalysis.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].KobayashiM,etal.InVitroantiretroviralpropertiesofS/GSK1349572,anext-generationHIVintegraseinhibitor.AntimicrobAgentsChemother.2011Feb;55(2):813-21.

    [2].MossL,etal.Thecomparativedispositionandmetabolismofdolutegravir,apotentHIV-1integraseinhibitor,inmice,rats,andmonkeys.Xenobiotica.2015Jan;45(1):60-70.

MolecularWeight

419.38

Formula

C₂₀H₁₉F₂N₃O₅

CASNo.

1051375-16-6

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:10mg/mL

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

Purity:99.54%