Antitumor activity of a novel nucleotide derivative, 5'-(1,2-dipalmitoyl-sn-glycero-3-phospho)-5-fluorouridine (TJ14026) on murine tumors.

Abstract

The antitumor activity of a nucleotide derivative, 5'-(1,2-dipalmitoyl-sn-glycero-3-phospho)-5-fluorouridine (TJ14026), was confirmed following both intraperitoneal and oral administration against a number of murine experimental tumor systems in vivo, which included Meth A fibrosarcoma, B16 melanoma, 5-fluorouracil (5-FU) resistant P388 leukemia, P815 mastocytoma and L5178Y-ML lymphoma. Successive i.p. injections of a small dose (10 mg/kg/d x 10) or intermittent i.p. injections of a larger dose (50 mg/kg/d x 3) were equally effective against the solid form of Meth A fibrosarcoma. Intraperitoneal injection of TJ14026 prolonged the life of mice with 5-FU resistant P388 leukemia. Oral administration of TJ14026 was also effective against P815 mastocytoma and L-5178Y-ML lymphoma in the liver, an P388 leukemia metastasized to the lymph nodes. Glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) levels were elevated in the serum of un-treated mice bearing P815 mastocytoma but not in mice treated with TJ14026.