Niraparib-MK-4827-DataSheet-生命科學試劑-MedChemExpress

Hotline:400-820-3792Inhibitors?ScreeningLibraries?Proteinswww.MedChemENiraparibCat.No.:HY-10619CASNo.:1038915-60-4Synonyms:MK-4827分?式:C??H??N?O分?量:320.39作?靶點:PARP;Apoptosis作?通路:CellCycle/DNADamage;Epigenetics;Apoptosis儲存?式:Powder-20°C3years4°C2yearsInsolvent-80°C6months-20°C1month溶解性數(shù)據(jù)體外實驗DMSO:25mg/mL(78.03mM;Needultrasonic)H2O:<0.1mg/mL(ultrasonic;warming;heatto80°C)(insoluble)MassSolvent1mg5mg10mgConcentration制備儲備液1mM3.1212mL15.6060mL31.2120mL5mM0.6242mL3.1212mL6.2424mL10mM0.3121mL1.5606mL3.1212mL請根據(jù)產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，避免反復凍融造成的產品失效。儲備液的保存?式和期限：-80°C,6months;-20°C,1month。-80°C儲存時，請在6個?內使?，-20°C儲存時，請在1個?內使?。體內實驗請根據(jù)您的實驗動物和給藥?式選擇適當?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：(為保證實驗結果的可靠性，澄的儲備液可以根據(jù)儲存條件，適當保存；體內實驗的?作液，建議您現(xiàn)?現(xiàn)配，當天使?；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：10%DMSO>>40%PEG300>>5%Tween-80>>45%salineSolubility:≥2.08mg/mL(6.49mM);Clearsolution2.請依序添加每種溶劑：10%DMSO>>90%(20%SBE-β-CDinsaline)Solubility:≥2.08mg/mL(6.49mM);Clearsolution3.請依序添加每種溶劑：10%DMSO>>90%cornoilSolubility:≥2.08mg/mL(6.49mM);ClearsolutionBIOLOGICALACTIVITY?物活性Niraparib(MK-4827)?效的，具有?物?服利?度的PARP1和PARP2抑制劑，IC50分別為3.8nM和2.1nM。Niraparib抑制DNA損傷修復，誘導凋亡(apoptosis)并具有抗腫瘤活性。IC50&TargetPARP-2PARP-1V-PARPTANK-12.1nM(IC50)3.8nM(IC50)330nM(IC50)570nM(IC50)PARP-31300nM(IC50)體外研究Niraparib(MK-4827)inhibitsPARPactivitywithEC50=4nMandEC90=45nMinawholecellassay.MK-4827inhibitsproliferationofcancercellswithmutantBRCA-1andBRCA-2withCC50inthe10-100nMrange.MK-4827displaysexcellentPARP1and2inhibitionwithIC50=3.8and2.1nM,respectively,andinawholecellassay[1].TovalidatethatNiraparib(MK-4827)inhibitsPARPinthesecelllines,A549andH1299cellsaretreatedwith1μMMK-4827forvarioustimesandmeasuredPARPenzymaticactivityusingachemiluminescentassay.TheresultsshowthatNiraparib(MK-4827)inhibitsPARPwithin15minutesoftreatmentreachingabout85%inhibitionintheA549cellsat1handabout55%inhibitionat1hfortheH1299cells[2].體內研究Niraparib(MK-4827)iswelltoleratedanddemonstratesefficacyasasingleagentinaxenograftmodelofBRCA-1deficientcancer.Niraparib(MK-4827)iswelltoleratedinvivoanddemonstratesefficacyasasingleagentinaxenograftmodelofBRCA-1deficientcancer.Niraparib(MK-4827)ischaracterizedbyacceptablepharmacokineticsinratswithplasmaclearanceof28(mL/min)/kg,veryhighvolumeofdistribution(Vdss=6.9L/kg),longterminalhalf-life(t1/2=3.4h),andexcellentbioavailability,F=65%[1].Niraparib(MK-4827)enhancesradiationresponseofp53mutantCalu-6tumorinbothcases,withthesingledailydoseof50mg/kgbeingmoreeffectivethan25mg/kggiventwicedaily[3].AnimalModel:Femalenudemice(NcrNu/Nu)withsolitarytumorxenografts[3]Dosage:25mg/kgor50mg/kgAdministration:Gavage,25mg/kgtwiceadaywith6hbetweendosesor50mg/kgoncedailyfor21consecutivedaysResult:Enhancedradiationresponse.2/3MasterofBioactiveMolecules—您?邊的抑制劑?師www.MedChemE戶使?本產品發(fā)表的科研?獻?CancerCell.2020Dec14;38(6):844-856.e7.?CancerDiscov.2017Sep;7(9):984-998.?JClinInvest.2019Mar1;129(3):1211-1228.?NatCommun.2022Nov19;13(1):7107.?AdvSci(Weinh).2022Oct;9(30):e2201210.Seemorecustomervalidationsonwww.MedChemEREFERENCES[1].JonesP,etal.Discoveryof2-{4-[(3S)-piperidin-3-yl]phenyl}-2H-indazole-7-carboxamide(MK-4827):anoveloralpoly(ADP-ribose)polymerase(PARP)inhibitorefficaciousinBRCA-1and-2mutanttumors.JMedChem.2009Nov26;52(22):7170-85.[2].BridgesKA,etal.Niraparib(MK-4827),anovelpoly(ADP-Ribose)polymeraseinhibitor,radiosensitizeshumanlungandbreastcancercells.Oncotarget.2014Jul15;5(13):5076-86.[3].WangL,etal.MK-4827,aPARP-1/-2inhibitor,stronglyenhancesresponseofhumanlungandbreastcancerxenograftstoradiation.InvestNewDrugs.2012Dec;30(6):2113-20.[4].MirzaMR,etal.NiraparibMaintenanceTherapyinPlatinum-Sensitive,RecurrentOvarianCancer.NEnglJMed.2016Dec1;375(22):2154