Kev piav qhia

Niraparib (MK-4827) yog ib qho muaj zog heev thiab hais lus bioavailable PARP1 thiab PARP2 inhibitor nrog IC50s ntawm 3.8 thiab 2.1 nM, feem. Niraparib ua rau inhibition ntawm kev kho DNA puas, activates apoptosis thiab qhia txog kev tiv thaiv qog.

Hauv Vitro

Niraparib (MK-4827) inhibits PARP kev ua haujlwm nrog EC50 = 4 nM thiab EC90 = 45 nM hauv tag nrho cov xov tooj ntawm tes. MK-4827 inhibits kev loj hlob ntawm cov qog nqaij hlav cancer nrog mutant BRCA-1 thiab BRCA-2 nrog CC50 hauv 10-100 nM ntau yam. MK-4827 qhia tau zoo heev PARP 1 thiab 2 inhibition nrog IC50 = 3.8 thiab 2.1 nM, raws li, thiab nyob rau hauv ib tug tag nrho cell assay[1]. Txhawm rau kom ntseeg tau tias Niraparib (MK-4827) inhibits PARP hauv cov kab ntawm tes, A549 thiab H1299 hlwb raug kho nrog 1.μM MK-4827 rau ntau lub sijhawm thiab ntsuas PARP enzymatic kev ua haujlwm siv cov tshuaj chemiluminescent. Cov txiaj ntsig tau pom tias Niraparib (MK-4827) inhibit PARP hauv 15 feeb ntawm kev kho mob mus txog 85% inhibition hauv A549 hlwb ntawm 1 h thiab txog 55% inhibition ntawm 1 h rau H1299 hlwb.

Niraparib (MK-4827) tau txais txiaj ntsig zoo thiab ua kom pom kev ua tau zoo raws li ib tus neeg sawv cev hauv xenograft qauv ntawm BRCA-1 tsis muaj mob qog noj ntshav. Niraparib (MK-4827) tau txais txiaj ntsig zoo hauv vivo thiab ua kom pom kev ua tau zoo raws li ib tus neeg sawv cev hauv xenograft qauv ntawm BRCA-1 tsis muaj mob qog noj ntshav. Niraparib (MK-4827) yog tus cwj pwm los ntawm kev siv tshuaj tua kab mob hauv cov nas tsuag nrog cov ntshav plasma clearance ntawm 28 (mL / min) / kg, ntau qhov ntim ntawm kev faib tawm (Vd_ss= 6.9 L / kg), ntev davhlau ya nyob twg ib nrab-lub neej (t_1/2= 3.4 h), thiab bioavailability zoo heev, F = 65%^[1]. Niraparib (MK-4827) txhim kho hluav taws xob teb ntawm p53 mutant Calu-6 qog nyob rau hauv ob qho tib si, nrog rau ib hnub koob tshuaj ntawm 50 mg / kg tau zoo tshaj 25 mg / kg muab ob zaug ib hnub twg.^].

Cia

Cov qauv tshuaj