Incazelo

I-Niraparib (MK-4827) inamandla kakhulu futhi itholakala ngomlomo nge-bioavailable PARP1 kanye ne-PARP2 inhibitor ene-IC50s ye-3.8 kanye ne-2.1 nM, ngokulandelanayo. I-Niraparib iholela ekuvinjweni kokulungiswa komonakalo we-DNA, isebenze i-apoptosis futhi ibonise umsebenzi wokulwa nesimila.

Ku-Vitro

I-Niraparib (MK-4827) ivimbela umsebenzi we-PARP nge-EC50=4 nM kanye ne-EC90=45 nM kuyo yonke i-cell assay. I-MK-4827 ivimbela ukwanda kwamaseli omdlavuza ane-BRCA-1 eguquguqukayo ne-BRCA-2 ene-CC50 ebangeni le-10-100 nM. I-MK-4827 ibonisa kahle kakhulu i-PARP 1 no-2 inhibition ene-IC50=3.8 kanye ne-2.1 nM, ngokulandelanayo, naku-assay yonke yeseli[1]. Ukuqinisekisa ukuthi i-Niraparib (MK-4827) ivimbela i-PARP kulayini weseli, amaseli e-A549 kanye ne-H1299 aphathwa ngo-1.μI-M MK-4827 yezikhathi ezihlukahlukene futhi ikalwe umsebenzi we-enzymatic we-PARP usebenzisa i-chemiluminescent assay. Imiphumela ibonisa ukuthi i-Niraparib (MK-4827) ivimbela i-PARP phakathi nemizuzu engu-15 yokwelashwa efinyelela cishe ukuvinjelwa kwe-85% kumaseli e-A549 ngehora elingu-1 kanye nokuvinjelwa okungama-55% ngehora elingu-1 kumaseli e-H1299.

I-Niraparib (MK-4827) ibekezelelwa kahle futhi ikhombisa ukusebenza kahle njenge-ejenti eyodwa kumodeli ye-xenograft ye-BRCA-1 yomdlavuza ongenawo. I-Niraparib (MK-4827) ibekezelelwa kahle ku-vivo futhi ikhombisa ukusebenza kahle njenge-ejenti eyodwa kumodeli ye-xenograft yomdlavuza oshodayo we-BRCA-1. I-Niraparib (MK-4827) ibonakala nge-pharmacokinetics eyamukelekayo kumagundane anemvume ye-plasma engu-28 (mL/min)/kg, umthamo omkhulu kakhulu wokusabalalisa (Vd_ss=6.9 L/kg), isigamu sempilo ende (t_1/2=3.4 h), kanye ne-bioavailability enhle kakhulu, F=65%^[1]. I-Niraparib (MK-4827) ithuthukisa ukusabela kwemisebe ye-p53 mutant Calu-6 tumor kuzo zombili izimo, ngomthamo owodwa wansuku zonke we-50 mg/kg usebenza kangcono kuno-25 mg/kg onikezwa kabili ngosuku.^].

Isitoreji

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