Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/2g-免疫在线蚂蚁淘旗下平台

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商品详细Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/2g

Medchemexpress/Olaparib（同义词：AZD2281；KU0059436）/HY-10162/2g

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

联系Q Q： 3392242852

电话号码： 4000-520-616

电子邮箱： info@ebiomall.com

立即询价

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

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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

ConcentrationVolumeMass	1mg	5mg	10mg

1mM	2.3017mL	11.5085mL	23.0171mL
5mM	0.4603mL	2.3017mL	4.6034mL
10mM	0.2302mL	1.1509mL	2.3017mL

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°C	3years
	4°C	2years
Insolvent	-80°C	6months
	-20°C	1month

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%

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