Sparfosic acid trisodium is a DNA antimetabolite agent and a potent inhibitor of aspartate transcarbamoyl transferase. Aspartate transcarbamoyl transferase catalyzes the second step of de novo pyrimidine biosynthesis. Sparfosic acid trisodium synergistically enhances the cytotoxicity of a combination of 5-fluorouracil (5-FU) and interferon-alpha (IFN) against human colon cancer cell lines[2].In Vitro: Sparfosic acid (N-(Phosphonacetyl)-L-aspartate, PALA) treatment causes apoptosis in the resistant Br1 cells.
Sparfosic acid (PALA, 300 μM) shows progressive accumulation of cells in S phase and activation of an apoptotic pathway leading to cell death.
In Vivo: Sparfosic acid (490 mg/kg; i.p.; on days 1, 5, and 9; mice bearing B16 melanoma) trisodium shows the life-span is increased survives 77 to 86% longer than controls. Lewis lung carcinoma is highly sensitive to Sparfosic acid trisodium. Treatment on days 1, 5, and 9 following s.c. implantation of Lewis lung carcinoma is curative to 50% of the mice.