| Biological Description |
Fludarabine Phosphate is an analogue of adenosine and deoxyadenosine, which is able to compete with dATP for incorporation into DNA and inhibit DNA synthesis.
IC50 Value: N/A
Target: DNA/RNA Synthesis
in vitro: Fludarabine Phosphate is converted to F-ara-ATP in cells and then incorporated into DNA in a self-limiting manner. Fludarabine Phosphate competes with dATP for incorporation into the A site of the extending DNA strand, which results in termination of DNA strand elongation. Human DNA polymerase alpha incorporates more Fludarabine Phosphate into DNA than polymerase delta. Fludarabine Phosphate completively inhibits DNA polymerase alpha and DNA polymerase delta with Ki of 1.1 uM and 1.3 uM, respectively. DNA polymerase delta is also able to excise the incorporated Fludarabine Phosphate from DNA in vitro.
in vivo: Fludarabine Phosphate is toxic for tumor-free mice. The maximum tolerated dose (LD10) Fludarabine Phosphate administered as a single dose is 234 mg/kg. The 50% lethal dose is 375 mg/kg. Fludarabine Phosphate administered as a single dose induces fewer number of cells surviving therapy in mice bearing P388 leukemia, accompanied by greater percentage of increase in life span (110%) and increased median survival time.
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