Ibisobanuro

Niraparib (MK-4827) ni 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 rya kanseri ya kanseri hamwe na BRCA-1 na BRCA-2 hamwe na CC50 mu ntera ya 10-100.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 ibihe bitandukanye kandi yapimye ibikorwa bya enzymatique ya PARP ukoresheje chemiluminescent.Ibisubizo byerekana ko Niraparib (MK-4827) ibuza PARP mu minota 15 yo kwivuza igera kuri 85% yabujijwe muri selile A549 kuri 1 h naho 55% ikabuza 1 h kuri selile H1299.

Niraparib (MK-4827) irihanganirwa kandi ikerekana imikorere nkumukozi umwe muburyo bwa xenograft ya kanseri yabuze BRCA-1.Niraparib (MK-4827) yihanganirwa neza muri vivo kandi yerekana imikorere nkumukozi umwe muburyo bwa xenograft ya 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 ya p53 mutant Calu-6 yibibyimba byombi, hamwe numunsi umwe wa 50 mg / kg ikora neza kurenza 25 mg / kg itangwa kabiri kumunsi^].

Ububiko

Imiterere yimiti