[Antitumor activity of a novel analog of cytarabine, 4-amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01)].

4-Amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01) was an orally active depot form of 1-beta-D-arabinofuranosylcytosine (Ara-C). In the present study, antitumor activity of YNK01 was compared with it of Ara-C in vitro and in vivo. The activity of a main metabolite of YNK01, 5'-carboxypropylphosphate of Ara-C (C-C3PCA), was also studied. Growth inhibitory activity of YNK01 against various cultured tumor cells was 1/32-1/1,100 of that of Ara-C. YNK01 exhibited antitumor activity against L1210 leukemia in mice after i.v., i.p. or p.o. administration. The activity did not depend on the administration routes. Compared with Ara-C, the activity was comparable in both i.v. and i.p. administrations, but greater in p.o. administration. Oral administration of YNK01 showed similar antitumor spectrum to i.p. administration of Ara-C. Oral activity of YNK01 against L1210 leukemia did not depend on the administration schedules but depended on a total administration dose. In contrast, activity of Ara-C greatly depended on the schedules, and the frequent i.p, administration showed greatest activity. Growth inhibitory activity of C-C3PCA against cultured tumor cells was 1/2-1/7 of Ara-C. The metabolite exhibited activity against L1210 leukemia in mice after i.p. administration. These results suggest that YNK01 is a clinically useful drug with p.o. administration for cancers as well as Ara-C.