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ʻO Niraparib (MK-4827) he mea hoʻomake nui loa a me ka waha bioavailable PARP1 a me PARP2 inhibitor me IC50s o 3.8 a me 2.1 nM, kēlā me kēia. Ke alakaʻi nei ʻo Niraparib i ka pale ʻana i ka hoʻoponopono ʻana i ka pōʻino DNA, hoʻāla i ka apoptosis a hōʻike i ka hana anti-tumor.

In Vitro

ʻO Niraparib (MK-4827) ke kāohi i ka hana PARP me EC50 = 4 nM a me EC90 = 45 nM i kahi ho'āʻo pūnaewele holoʻokoʻa. Kāohi ʻo MK-4827 i ka hoʻonui ʻia ʻana o nā pūnaʻi maʻi maʻi me ka mutant BRCA-1 a me BRCA-2 me CC50 ma ka laulā 10-100 nM. Hōʻike ʻo MK-4827 i ka PARP 1 a me 2 inhibition maikaʻi loa me IC50 = 3.8 a me 2.1 nM, kēlā me kēia, a i loko o kahi hōʻike cell holoʻokoʻa [1]. No ka hōʻoia ʻana i ka Niraparib (MK-4827) ke kāohi i ka PARP i kēia mau laina kelepona, mālama ʻia nā cell A549 a me H1299 me 1μM MK-4827 no nā manawa like ʻole a ua ana i ka hana enzymatic PARP me ka hoʻohana ʻana i kahi hoʻokolohua chemiluminescent. Hōʻike nā hopena i ka Niraparib (MK-4827) kaohi i ka PARP i loko o 15 mau minuke o ka mālama ʻana a hiki i kahi 85% inhibition i nā cell A549 ma 1 hola a ma kahi o 55% inhibition ma 1 h no nā cell H1299.

Ua ʻae maikaʻi ʻia ʻo Niraparib (MK-4827) a hōʻike i ka maikaʻi ma ke ʻano he mea hoʻokahi i kahi hoʻohālike xenograft o BRCA-1 deficient cancer. Ua ʻae maikaʻi ʻia ʻo Niraparib (MK-4827) i loko o vivo a hōʻike i ka maikaʻi ma ke ʻano he mea hoʻokahi i loko o kahi kumu xenograft o BRCA-1 deficient cancer. Hōʻike ʻia ʻo Niraparib (MK-4827) e nā pharmacokinetics i ʻae ʻia i nā ʻiole me ka hoʻomaʻemaʻe plasma o 28 (mL/min)/kg, kiʻekiʻe kiʻekiʻe o ka hāʻawi ʻana (Vd._ss=6.9 L/kg), ka hapalua o ke ola hope loa (t_1/2=3.4 h), a me ka bioavailability maikaʻi loa, F=65%^[1]. Hoʻonui ʻo Niraparib (MK-4827) i ka pane radiation o ka p53 mutant Calu-6 tumo ma nā hihia ʻelua, me ka ʻoi aku o ka hopena o kēlā me kēia lā o 50 mg/kg ma mua o 25 mg/kg i hāʻawi ʻia ʻelua i kēlā me kēia lā.^].

Waihona

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