Fludarabine Phosphate (NSC 312887 Phosphate) is the phosphate salt of a fluorinated nucleotide antimetabolite analog of the antiviral agent vidarabine (ara-A) with antineoplastic activity. Fludarabine phosphate is rapidly dephosphorylated to 2-fluoro-ara-A and then phosphorylated intracellularly by deoxycytidine kinase to the active triphosphate, 2-fluoro-ara-ATP. This metabolite may inhibit DNA polymerase alpha, ribonucleotide reductase, and DNA primase, thereby interrupting DNA synthesis and inhibiting tumor cell growth.

DNA polymerase α:1.1 μM(Ki ), DNA polymerase δ:1.3 μM(Ki)

Fludarabine Phosphate的最大耐受剂量为234 mg/kg.Fludarabine对小鼠的LD50为375 mg/kg.Fludarabine Phosphate对于无肿瘤的小鼠有毒性.在携带P388白血病的小鼠中,Fludarabine Phosphate可诱导细胞存活治疗的数量减少,寿命更大比例地增加110％,平均存活时间增加.

Fludarabine Phosphate完全抑制DNA聚合酶α/δ（Ki：1.1/1.3 μM）。在体外,DNA聚合酶δ可将Fludarabine Phosphate从结合的DNA上切除。Fludarabine Phosphate与三磷酸脱氧腺苷竞争性地结合到延伸DNA链的A位点,使DNA链延伸的终止人DNA聚合酶α比δ更能将Fludarabine Phosphate结合到DNA中。

Cells are incubated with Fludarabine Phosphate for 5 hr and washed twice with drug-free warm medium. 800 cells are mixed with 1.3 mL of 0.25% soft agar in Dulbecco's medium supplemented with 20% fetal bovine serum (pre-warmed to 37 ℃) and incubated in a tissue culture dish for 10 days (humidified 5% CO2 , 37 ℃). At the end of the incubation period, colonies of more than 40 cells are scored under a microscope. The cytotoxic effect of the drugs is expressed as a percentage of survival relative to that of untreated control cells.(Only for Reference)