title: [Antitumor activity of a novel analog of cytarabine, 4-amino-1-beta-D-arabinofuranosyl-2(1H)-pyrimidinone 5'-(sodium octadecyl phosphate) monohydrate (YNK01)].
abstract: 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.
authors.affiliation: Research Laboratories, Pharmaceuticals Group, Nippon Kayaku Co., Ltd.
authors.forename: T
authors.initials: T
authors.lastname: Nagahata
authors.forename: C
authors.initials: C
authors.lastname: Shibasaki
authors.forename: T
authors.initials: T
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Uchida
authors.forename: M
authors.initials: M
authors.lastname: Arakawa
authors.forename: K
authors.initials: K
authors.lastname: Kusama
authors.forename: H
authors.initials: H
authors.lastname: Ekimoto
authors.forename: K
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D001088:Arabinonucleotides / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003561:Cytarabine / Q000494:pharmacology; D003568:Cytidine Monophosphate / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D004334:Drug Administration Schedule; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007939:Leukemia L1210 / Q000188:drug therapy; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D001088:Arabinonucleotides; D003597:Cytosine Nucleotides; D003561:Cytarabine; C061162:1-arabinofuranosylcytosine-5'-stearylphosphate; C065414:cytarabine 5'-carboxypropylphosphate; D003568:Cytidine Monophosphate