Tlhaloso

Niraparib (MK-4827) ke PARP1 le PARP2 inhibitor e matla haholo ebile e fumaneha ka molomo ka IC50s ea 3.8 le 2.1 nM, ka ho latellana. Niraparib e lebisa ho thibela ho lokisoa ha tšenyo ea DNA, e kenya tšebetsong apoptosis mme e bonts'a ts'ebetso ea anti-tumor.

Ka Vitro

Niraparib (MK-4827) e thibela tšebetso ea PARP ka EC50=4 nM le EC90=45 nM tlhahlobong eohle ea lisele. MK-4827 e thibela ho ata ha lisele tsa mofetše tse nang le BRCA-1 e fetotsoeng le BRCA-2 e nang le CC50 ho 10-100 nM range. MK-4827 e bonts'a thibelo e ntle ea PARP 1 le 2 ka IC50=3.8 le 2.1 nM, ka ho latellana, le tlhahlobong eohle ea lisele[1]. Ho netefatsa hore Niraparib (MK-4827) e thibela PARP meleng ena ea lisele, lisele tsa A549 le H1299 li tšoaroa ka 1.μM MK-4827 bakeng sa linako tse fapaneng mme e lekantsoe ts'ebetso ea enzymatic ea PARP e sebelisa tlhahlobo ea chemiluminescent. Liphello li bontša hore Niraparib (MK-4827) e thibela PARP ka hare ho metsotso ea 15 ea phekolo e fihlang hoo e ka bang 85% ea ho thibela lisele tsa A549 ka 1 h le hoo e ka bang 55% e thibelang ho 1 h bakeng sa lisele tsa H1299.

Niraparib (MK-4827) e mamelloa hantle 'me e bontša katleho e le moemeli a le mong mofuteng oa xenograft oa mofets'e o haellang oa BRCA-1. Niraparib (MK-4827) e mamelloa hantle ka har'a vivo mme e bonts'a katleho e le moemeli a le mong mofuteng oa xenograft oa mofets'e o haellang oa BRCA-1. Niraparib (MK-4827) e tšoauoa ka pharmacokinetics e amohelehang ho likhoto tse nang le tumello ea plasma ea 28 (mL / min) / kg, palo e phahameng haholo ea kabo (Vd)._ss= 6.9 L/kg), halofo ea bophelo e telele (t_1/2=3.4 h), le bioavailability e babatsehang, F=65%^[1]. Niraparib (MK-4827) e ntlafatsa karabelo ea mahlaseli a hlahala ea p53 e feto-fetohang ea Calu-6 maemong ao ka bobeli, ka tekanyetso e le 'ngoe ea letsatsi le letsatsi ea 50 mg/kg e sebetsa ho feta 25 mg/kg e fanoang habeli ka letsatsi.^].

Polokelo

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