Veliparib-dihydrochloride-ABT-888-dihydrochloride-DataSheet-生命科學(xué)試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemEVeliparibdihydrochlorideCat.No.:HY-10130CASNo.:912445-05-7Synonyms:ABT-888dihydrochloride分?式:C??H??Cl?N?O分?量:317.21作?靶點:PARP;Autophagy作?通路:CellCycle/DNADamage;Epigenetics;Autophagy儲存?式:4°C,sealedstorage,awayfrommoisture*Insolvent:-80°C,6months;-20°C,1month(sealed

storage,awayfrommoisture)溶解性數(shù)據(jù)體外實驗H2O:250mg/mL(788.12mM;Needultrasonic)DMSO:≥3.2mg/mL(10.09mM)*"≥"meanssoluble,butsaturationunknown.MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.1525mL15.7624mL31.5249mL5mM0.6305mL3.1525mL6.3050mL10mM0.3152mL1.5762mL3.1525mL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(fù)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(sealedstorage,awayfrommoisture)。-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(dāng)?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(dāng)保存；體內(nèi)實驗的?作液，建議您現(xiàn)?現(xiàn)配，當(dāng)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：PBSSolubility:100mg/mL(315.25mM);Clearsolution;NeedultrasonicBIOLOGICALACTIVITY?物活性Veliparibdihydrochloride有效的PARP1和PARP2抑制劑，Ki分別為5.2nM，2.9nM。IC50&TargetPARP-2PARP-12.9nM(Ki)5.2nM(Ki)體外研究VeliparibisinactivetoSIRT2(>5μM)[1].VeliparibinhibitsthePARPactivitywithEC50of2nMinC41cells[2].VeliparibcandecreasethePARlevelsinbothirradiatedandnonirradiatedH460cells.VeliparibreducesclonogenicsurvivalandinhibitsDNArepairbyPARP-1inhibitioninH460cells.VeliparibincreasesapoptosisandautophagyinH460cellswhencombinationwithradiation[3].VeliparibinhibitsPARPactivityinH1299,DU145and22RV1cellsandtheinhibitionisindependentofp53function.Veliparib(10μM)suppressesthesurvivingfraction(SF)by43%intheclonogenicH1299cells.VeliparibshowseffectiveradiosensitivityinoxicH1299cells.VeliparibcanattenuatetheSFofhypoxic-irradiatedcellsincludingH1299,DU145and22RV1[4].體內(nèi)研究TheoralbioavailabilityofVeliparibis56%-92%inmice,SDrats,beagledogs,andcynomolgusmonkeysafteroraladministration[1].Veliparib(25mg/kg,i.p.)canimprovetumorgrowthdelayinaNCI-H460xenograftmodel.Combinationwithradiation,veliparibdecreasesthetumorvesselformation[3].VeliparibreducesintratumorPARlevelsbymorethan95%atadoseof3and12.5mg/kginA375andColo829xenograftmodelsandthesuppressioncanbemaintainedovertime[4].PROTOCOLKinaseAssay[1]PARPassaysareconductedinabuffercontaining50mMTris(pH8.0),1mMDTT,1.5μM[3H]NAD+(1.6μCi/mmol),200nMbiotinylatedhistoneH1,200nMslDNA,and1nMPARP-1or4nMPARP-2enzyme.Reactionsareterminatedwith1.5mMbenzamide,transferredtostreptavidinFlashplates,andcountedusingaTopCountmicroplatescintillationcounter.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.AnimalForB16F10syngeneicstudies,6×104cellsaremixedwith50%Matrigelandinoculatedbys.c.injectionintoAdministration[1]theflankof6-to8-week-oldfemaleC57BL/6mice(20g).Forcisplatinefficacystudies,femalenudemiceareimplanteds.c.bytrocarwithfragments(20-30mm3)ofhumantumorsharvestedfroms.c.growntumorsinnudemicehosts.ForthecarboplatinandMX-1cyclophosphamidestudies,femalescidmiceareinoculatedwith200μLofa1:10dilutionoftumorbreiin45%Matrigeland45%SpinnerMEM.Fortheseestablishedtumorstudies,tumorsareallowedtogrowtotheindicatedsizeandthenrandomizedtotherapygroups.ForDOHH-2xenograftstudies,1×106cellsaremixedwith50%Matrigelandinoculatedbys.c.injectionintotheflankofmalescidmice.Veliparibisdeliveredbyeitheroralrouteorcontinuousinfusionusings.c.placementof14-dayAlzetOMPmodel2002inavehiclecontaining0.9%NaCladjustedtopH4.0.TheOMPdeliversat2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemEarateof12μLdailyandVeliparibdosesarecalculatedaccordingly.Temozolomide,cisplatin,carboplatin,andcyclophosphamideareformulatedaccordingtothemanufacturers'recommendations.MCEhasnotindependentlyconfirmedtheaccuracyofthesemethods.Theyareforreferenceonly.戶使?本產(chǎn)品發(fā)表的科研?獻(xiàn)?CancerDiscov.2017Sep;7(9):984-998.?NatCommun.2021Jun24;12(1):3931.?ClinCancerRes.2017Feb15;23(4):1001-1011.?Theranostics.2020Jul25;10(21):9477-9494.?Oncogene.2022Aug6.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].DonawhoCK,etal.ABT-888,anorallyactivepoly(ADP-ribose)polymeraseinhibitorthatpotentiatesDNA-damagingagentsinpreclinicaltumormodels.ClinCancerRes.2007May1;13(9):2728-37.[2].PenningTD,etal.DiscoveryofthePoly(ADP-ribose)polymerase(PARP)inhibitor2-[(R)-2-methylpyrrolidin-2-yl]-1H-benzimidazole-4-carboxamide(ABT-888)forthetreatmentofcancer.JMedChem.2009Jan22;52(2):514-23.[3].AlbertJM,etal.Inhibitionofpoly(ADP-ribose)polymeraseenhancescelldeathandimprovestumorgrowthdelayinirradiatedlungcancermodels.ClinCancerRes.2007May15;13(10):3033-42.[4].RobertJ.Kinders,etal.PreclinicalModelingofaPhase0ClinicalTrial:QualificationofaPharmacodynamicAssayofPoly(ADP-Ribose)PolymeraseinTumorBiopsiesofMouseXenografts.