Fa'amatalaga

O le Niraparib (MK-4827) o se mea e sili ona malosi ma faʻaogaina faʻamalama PARP1 ma PARP2 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 gaioiga anti-tumor.

I Vitro

Niraparib (MK-4827) faʻalavelaveina le PARP gaioiga ma EC50 = 4 nM ma EC90 = 45 nM i se suʻega sela 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) faʻalavelaveina le PARP i totonu ole 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 lelei le faʻafeiloaʻi 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 faʻafeiloaʻi lelei i vivo 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) 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'ato'a afa ola (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, faatasi 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