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当前位置： 首页 > 产品中心 > Small_molecule > Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/500mg
商品详细Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/500mg
Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/500mg
Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/500mg
商品编号： HY-10162-10mM*1mLinDMSO
品牌： MedChemExp
市场价： ¥1320.00
美元价： 792.00
产地： 美国(厂家直采)
公司：
产品分类： 小分子
公司分类： Small_molecule
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商品介绍
OlaparibisapotentPARPinhibitorwithIC50of5and1nMforPARP-1andPARP-2,respectively.

CustomerValidation

  • •CancerDiscov.2017Sep;7(9):984-998.
  • •ClinCancerRes.2017Feb15;23(4):1001-1011.
  • •Oncogene.2017Sep25.
  • •IntJMolSci.2016Feb24;17(3):272.
  • •IntJMolSci.2015Oct19;16(10):24820-38.
  • •EurJPharmacol.2017Nov15;815:147-155.
  • •CancerChemotherPharmacol.2017Oct;80(4):861-867.
  • •HarvardMedicalSchoolLINCSLIBRARY
Description

OlaparibisapotentPARPinhibitorwithIC50of5and1nMforPARP-1andPARP-2,respectively.

IC50&Target

IC50:5/1nM(PARP-1/2)[1]

InVitro

Olaparib(AZD2281)isasingledigitnanomolarinhibitorofbothPARP-1andPARP-2thatshowsstandaloneactivityagainstBRCA1-deficientbreastcancercelllines.OlaparibisappliedtoSW620celllysates,andidentifiedtheIC50forPARP-1inhibitiontobearound6nMandthetotalablationofPARP-1activitytobeatconcentrationsof30−100nM[1].

InVivo

AnimalsbearingSW620xenograftedtumorsaretreatedwithOlaparib(10mg/kg,p.o.)incombinationwithTemozolomide(TMZ)(50mg/kg,p.o.)oncedailyfor5consecutivedays,afterwhichthetumorsarelefttogrowout[1].OlaparibincreasesvascularperfusioninCalu-6tumorsestablishedinaDWCmodel.AdmiNISTrationofolaparib(50mg/kg,p.o.)asasingleagent(toppanel)orincombinationwithrADIation(bottompanel)resultsinanincreaseinfluorescenceintensityintheCalu-6tumors[2].

ClinicalTrial
ViewMoreCollapse
References

  • [1].MenearKA,etal.4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one:anovelbioavailableinhibitorofpoly(ADP-ribose)polymerase-1.JMedChem.2008Oct23;51(20):6581-91

    [2].SenraJM,etal.InhibitionofPARP-1byolaparib(AZD2281)increasestheradiosensitivityofalungtumorxenograft.MolCancerTher.2011Oct;10(10):1949-58.

    [3].YasukawaM,etal.SynergeticEffectsofPARPInhibitorAZD2281andCisplatininOralSquamousCellCarcinomainVitroandinVivo.IntJMolSci.2016Feb24;17(3):272.

    [4].BianX,etal.PTENdeficiencysensitizesendometrioidendometrialcancertocompoundPARP-PI3KinhibitionbutnotPARPinhibitionasmonotherapy.Oncogene.2017Sep25.

PreparingStockSolutions
ConcentrationVolumeMass1mg5mg10mg
1mM2.3017mL11.5085mL23.0171mL
5mM0.4603mL2.3017mL4.6034mL
10mM0.2302mL1.1509mL2.3017mL
Pleaserefertothesolubilityinformationtoselecttheappropriatesolvent.
KinaseAssay
[1]

ThisassaydeterminedtheABIlityofOlaparibtoinhibitPARP-1enzymeactivity.PARP-2activityinhibitionismeasuredbyusingavariationofthePARP-1assayinwhichPARP-2protein(recombinant)isbounddownbyaPARP-2specificantibodyina96-wellwhite-walledplate.PARP-2activityismeasuredfollowing3H-NAD+DNAadditions.Afterwashing,scintillantisaddedtomeasure3H-incorporatedribosylations.Fortankyrase-1,anAlphaScreenassayisdevelopedinwhichHIS-taggedrecombinantTANK-1proteinisincubatedwithbiotinylatedNAD+ina384-wellProxiPlateassay.AlphabeadsareaddedtobindtheHISandbiotintagstocreateaproximitysignal,whereastheinhibitionofTANK-1activityisdirectlyproportionaltothelossofthissignal.Allexperimentsarerepeatedatleastthreetimes[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

CellAssay
[1]

OlaparibisdissolvedinDMSOandstored,andthendilutedwithappropriatemediabeforeuse[1].

ThePF50valueisthepotentiationfactor,whichiscalculatedastheratiooftheIC50ofthecontrolgrowthwithalkylatingagentmethylmethanesulfonate(MMS)dividedbytheIC50oftheMMScombinedwiththePARPinhibitor.HeLaBcellsareused,andOlaparibistestedatafixed200nMconcentrationforscreeningwithMMS.ForthetestingofOlaparibontheSW620colorectalcellline,theconcentrationsthatareusedare1,3,10,100and300nM.CellgrowthisassessedbytheuseofthesulforhodamineB(SRB)assay[1].MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

AnimalAdministration
[2]

OlaparibispreparedinPBS(containing10%DMSOand10%2-hydroxy-propyl-β-cyclodextrin)(Mice)[2].

Mice[2]
Micebearing220-250mm3tumorsarerandomizedinto4treatmentgroups(n=5):A;vehiclecontrol(10%DMSOinPBS/10%2-hydroxy-propyl-β-cyclodextrindailyfor5daysbyoralgavage),B;Olaparib(50mg/kgdailyfor5daysbyoralgavage),C;10Gyfractionatedradiotherapy(2Gydailyfor5days),D;Olapariband10Gy(5×2Gy)fractionatedradiotherapy(witholaparibgiven30minpriortoeachdaily2Gydoseofradiation).Tumorvolumemeasurementsaredetermineddailyuntiltheyreached1000mm3.Thenumberofdaysforeachindividualtumortoquadrupleinsizefromthestartofthetreatment(relativetumorvolume×4;RTV4)iscalculatedfortheindividualtumorsineachgroup.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.

References

  • [1].MenearKA,etal.4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one:anovelbioavailableinhibitorofpoly(ADP-ribose)polymerase-1.JMedChem.2008Oct23;51(20):6581-91

    [2].SenraJM,etal.InhibitionofPARP-1byolaparib(AZD2281)increasestheradiosensitivityofalungtumorxenograft.MolCancerTher.2011Oct;10(10):1949-58.

    [3].YasukawaM,etal.SynergeticEffectsofPARPInhibitorAZD2281andCisplatininOralSquamousCellCarcinomainVitroandinVivo.IntJMolSci.2016Feb24;17(3):272.

    [4].BianX,etal.PTENdeficiencysensitizesendometrioidendometrialcancertocompoundPARP-PI3KinhibitionbutnotPARPinhibitionasmonotherapy.Oncogene.2017Sep25.

MolecularWeight

434.46

Formula

C₂₄H₂₃FN₄O₃

CASNo.

763113-22-0

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

RoomtemperatureincontinentalUS;mayvaryelsewhere

Solvent&Solubility

DMSO:29mg/mL

invivo:OlaparibisdissolvedinDMSO(31.25mg/mL)andthendilutedwithPBS(DMSO:PBS=1:9).
Olaparib(AZD2281)isdissolvedin200µLsterilizedwater)[3].
Olaparibisdissolvedin10%hydroxypropyl-β-Cyclodextrinanddosedat50 mg/kgperday(i.p.)[4].

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

References

  • [1].MenearKA,etal.4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one:anovelbioavailableinhibitorofpoly(ADP-ribose)polymerase-1.JMedChem.2008Oct23;51(20):6581-91

    [2].SenraJM,etal.InhibitionofPARP-1byolaparib(AZD2281)increasestheradiosensitivityofalungtumorxenograft.MolCancerTher.2011Oct;10(10):1949-58.

    [3].YasukawaM,etal.SynergeticEffectsofPARPInhibitorAZD2281andCisplatininOralSquamousCellCarcinomainVitroandinVivo.IntJMolSci.2016Feb24;17(3):272.

    [4].BianX,etal.PTENdeficiencysensitizesendometrioidendometrialcancertocompoundPARP-PI3KinhibitionbutnotPARPinhibitionasmonotherapy.Oncogene.2017Sep25.

Purity:99.71%