Kufotokozera

Niraparib (MK-4827) ndi yamphamvu kwambiri komanso yopezeka pakamwa PARP1 ndi PARP2 inhibitor yokhala ndi IC50s ya 3.8 ndi 2.1 nM, motsatana. Niraparib imayambitsa kuletsa kukonzanso kwa kuwonongeka kwa DNA, imayambitsa apoptosis ndikuwonetsa zochita zotsutsana ndi chotupa.

Mu Vitro

Niraparib (MK-4827) imalepheretsa zochitika za PARP ndi EC50=4 nM ndi EC90=45 nM mu kuyesa konse kwa cell. MK-4827 imalepheretsa kuchuluka kwa maselo a khansa omwe ali ndi BRCA-1 osasinthika ndi BRCA-2 okhala ndi CC50 mumtundu wa 10-100 nM. MK-4827 imawonetsa bwino kwambiri PARP 1 ndi 2 zoletsa ndi IC50 = 3.8 ndi 2.1 nM, motsatana, komanso pama cell assay[1]. Kuti atsimikizire kuti Niraparib (MK-4827) imaletsa PARP m'maselo awa, maselo a A549 ndi H1299 amathandizidwa ndi 1.μM MK-4827 kwa nthawi zosiyanasiyana ndikuyesa ntchito ya PARP enzymatic pogwiritsa ntchito chemiluminescent assay. Zotsatira zimasonyeza kuti Niraparib (MK-4827) imalepheretsa PARP mkati mwa mphindi za 15 za chithandizo chofikira pafupifupi 85% kulepheretsa m'maselo a A549 pa 1 h ndi pafupifupi 55% kuletsa pa 1 h kwa maselo a H1299.

Niraparib (MK-4827) imalekerera bwino ndipo ikuwonetsa kuthandizira ngati wothandizira m'modzi mu mtundu wa xenograft wa khansa yoperewera ya BRCA-1. Niraparib (MK-4827) imaloledwa bwino mu vivo ndipo ikuwonetsa kuthandizira ngati wothandizira m'modzi mu mtundu wa xenograft wa khansa yoperewera ya BRCA-1. Niraparib (MK-4827) imadziwika ndi ma pharmacokinetics ovomerezeka mu makoswe okhala ndi chilolezo cha plasma cha 28 (mL/min)/kg, kugawa kwakukulu kwambiri (Vd)._ss= 6.9 L/kg), theka la moyo wautali (t_1/2=3.4 h), komanso bioavailability yabwino kwambiri, F=65%^[1]. Niraparib (MK-4827) imathandizira kuyankhidwa kwa radiation kwa p53 mutant Calu-6 chotupa muzochitika zonsezi, ndi mlingo umodzi watsiku ndi tsiku wa 50 mg/kg umakhala wothandiza kuposa 25 mg/kg woperekedwa kawiri tsiku lililonse.^].

Kusungirako

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