Ibisobanuro

Niraparib (MK-4827) ni imbaraga zikomeye kandi mu kanwa bioavailable PARP1 na PARP2 inhibitor hamwe na IC50s ya 3.8 na 2.1 nM. Niraparib itera kubuza gusana ibyangiritse kuri ADN, ikora apoptose kandi ikerekana ibikorwa byo kurwanya ibibyimba.

Muri Vitro

Niraparib (MK-4827) ibuza ibikorwa bya PARP hamwe na EC50 = 4 nM na EC90 = 45 nM muri selile yose. MK-4827 ibuza ikwirakwizwa ry'uturemangingo twa kanseri hamwe na mutant BRCA-1 na BRCA-2 hamwe na CC50 mu ntera ya 10-100 nM. MK-4827 yerekana PARP 1 na 2 nziza cyane hamwe na IC50 = 3.8 na 2.1 nM, hamwe no muri selile yose [1]. Kwemeza ko Niraparib (MK-4827) ibuza PARP muriyi mirongo, selile A549 na H1299 zivurwa hamwe na 1μM MK-4827 mu bihe bitandukanye kandi yapimye ibikorwa byimisemburo ya PARP ukoresheje chemiluminescent. Ibisubizo byerekana ko Niraparib (MK-4827) ibuza PARP mu minota 15 yo kwivuza igera kuri 85% yabujijwe mu tugari A549 saa 1 h naho hafi 55% yabujijwe kuri 1 h kuri selile H1299.

Niraparib (MK-4827) irihanganirwa kandi ikerekana imikorere nkumukozi umwe muburyo bwa xenograft bwerekana kanseri yabuze BRCA-1. Niraparib (MK-4827) yihanganirwa neza muri vivo kandi yerekana imikorere nkumukozi umwe muburyo bwa xenograft bwerekana kanseri yabuze BRCA-1. Niraparib (MK-4827) irangwa na farumasi yemewe yimbeba nimbeba zifite plasma ya 28 (mL / min) / kg, ubwinshi bwikwirakwizwa (Vd_ss= 6.9 L / kg), uburebure burebure igice cyubuzima (t_1/2= 3.4 h), hamwe na bioavailable nziza, F = 65%^[1]. Niraparib (MK-4827) yongerera imbaraga imishwarara yibibyimba bya p53 mutant Calu-6 muri ibyo bihe byombi, ikinini kimwe cya buri munsi cya 50 mg / kg kiba cyiza kuruta mg / kg 25 gitangwa kabiri kumunsi^].

Ububiko

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