Research Area: Cancer
Biological Activity:
Fludarabine Phosphate (Fludara) is a nucleoside analogue and formulated as the monophosphate form of F-ara-AMP(fludarabine, IC50 < 3 μM). To enhance solubility, Fludara is formulated as the monophosphate (F-ara-AMP, fudarabine), which is instantaneously and quantitatively dephosphorylated to the parent nucleoside upon intravenous infusion. Inside the cells rephosphorylation occurs which leads to fuoroadenine arabinoside triphosphate (F-ara-ATP),the major cytotoxic metabolite of F-ara-A. This metabolite inhibits several key processes necessary for the DNA replication, i.e. enzymes required in the DNA synthesis, such as ribonucleotide reductase, DNA primase, DNA polymerase, 3’-5’ exonuclease activity of DNA polymerase d and e and DNA ligase I. [1] Fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. [2] Fludarabine did not affect the growth of ovarian cancer cell lines, whereas it induced a marked and dose-dependent inhibition of proliferation in melanoma cell lines. [3] |