Fa'amatalaga

O le Niraparib (MK-4827) o se PARP1 ma le PARP2 e sili ona malosi ma tuʻu tautala faʻatasi ma IC50s o le 3.8 ma le 2.1 nM, i le faasologa.Niraparib e taʻitaʻia ai le taofiofia o le toe faʻaleleia o DNA faʻaleagaina, faʻagaoioia apoptosis ma faʻaalia ai le anti-tumor.

I Vitro

Niraparib (MK-4827) faʻalavelaveina le PARP faʻatasi ma EC50 = 4 nM ma EC90 = 45 nM i se suʻega suʻega atoa.MK-4827 fa'alavelaveina le fa'atuputeleina o sela o le kanesa ma mutant BRCA-1 ma BRCA-2 fa'atasi ma CC50 i le va'aiga 10-100 nM.MK-4827 faʻaalia lelei PARP 1 ma 2 faʻalavelave faʻatasi ma le IC50 = 3.8 ma le 2.1 nM, faʻasologa, ma i totonu o se suʻega sela atoa [1].Ina ia faʻamaonia o le Niraparib (MK-4827) faʻalavelaveina le PARP i nei laina sela, o le A549 ma le H1299 sela e togafitia i le 1μM MK-4827 mo taimi eseese ma fuaina galuega enzymatic PARP e faʻaaoga ai se suʻega chemiluminescent.O faʻaiʻuga o loʻo faʻaalia ai o Niraparib (MK-4827) faʻalavelave le PARP i totonu o le 15 minute o togafitiga e oʻo atu i le 85% faʻalavelave i le A549 sela i le 1 itula ma le 55% faʻalavelave ile 1 h mo le H1299 sela.

Niraparib (MK-4827) e faʻafeiloaʻi lelei ma faʻaalia le aoga o se sui e tasi i se xenograft faʻataʻitaʻiga o le BRCA-1 e le atoatoa le kanesa.Niraparib (MK-4827) e talia lelei i vivo ma faʻaalia le aoga o se sui e tasi i se xenograft faʻataʻitaʻiga o le BRCA-1 le atoatoa o le kanesa.Niraparib (MK-4827) o loʻo faʻaalia e pharmacokinetics taliaina i isumu ma le kilia plasma o le 28 (mL / min) / kg, maualuga tele le tufatufaina atu (Vd)._ss=6.9 L/kg), umi fa'agata fa'amamafa (t_1/2=3.4 h), ma sili ona lelei bioavailability, F=65%^[1].Niraparib (MK-4827) faʻaleleia le tali atu o le radiation o le p53 mutant Calu-6 tumo i tulaga uma e lua, faʻatasi ai ma le fua tasi aso o le 50 mg / kg e sili atu le aoga nai lo le 25 mg / kg tuʻuina faalua i aso taitasi^].

Teuina

Fa'asologa o vaila'au