Nkọwa

Niraparib (MK-4827) bụ ihe dị ike na ọnụ nke nwere ike ịdị ndụ PARP1 na PARP2 inhibitor nwere IC50s nke 3.8 na 2.1 nM, n'otu n'otu. Niraparib na-eduga na mgbochi nke mmezi nke DNA mebiri emebi, na-eme ka apoptosis rụọ ọrụ ma gosipụta ọrụ mgbochi tumor.

Na Vitro

Niraparib (MK-4827) na-egbochi ọrụ PARP na EC50 = 4 nM na EC90 = 45 nM na nyocha sel dum. MK-4827 na-egbochi mmụba nke mkpụrụ ndụ kansa nke nwere BRCA-1 na BRCA-2 nwere CC50 na 10-100 nM. MK-4827 na-egosiputa mmachi PARP 1 na 2 na IC50 = 3.8 na 2.1 nM, n'otu n'otu, yana nyocha mkpụrụ ndụ dum[1]. Iji kwado na Niraparib (MK-4827) na-egbochi PARP na ahịrị sel ndị a, a na-eji mkpụrụ ndụ A549 na H1299 1.μM MK-4827 maka oge dị iche iche ma tụọ ọrụ enzymatic PARP site na iji nyocha chemiluminescent. Nsonaazụ gosiri na Niraparib (MK-4827) na-egbochi PARP n'ime nkeji iri na ise nke ọgwụgwọ na-eru ihe dị ka 85% mgbochi na sel A549 na 1 h na ihe dịka 55% mgbochi na 1 h maka sel H1299.

Niraparib (MK-4827) na-anabata nke ọma ma gosipụta ịdị irè dị ka otu onye nnọchi anya na ụdị xenograft nke ọrịa cancer na-adịghị BRCA-1. Niraparib (MK-4827) na-anabata nke ọma na vivo ma gosipụta ịdị irè dị ka otu onye nnọchi anya n'ụdị xenograft nke ọrịa cancer na-adịghị BRCA-1. A na-eji Niraparib (MK-4827) site na ọgwụ pharmacokinetics a na-anabata na oke nwere mkpochapụ plasma nke 28 (mL / min) / kg, oke oke nkesa (Vd)._ss= 6.9 L/kg), ogologo ndụ ọkara ndụ (t_1/2= 3.4 h), na ezigbo bioavailability, F=65%^[1]. Niraparib (MK-4827) na-akwalite nzaghachi radieshon nke p53 mutant Calu-6 tumor n'ọnọdụ abụọ ahụ, yana otu dose kwa ụbọchị nke 50 mg / kg na-adị irè karịa 25 mg / kg nyere ugboro abụọ kwa ụbọchị.^].

Nchekwa

Ọdịdị chemical