Background:

Fludarabine is a purine analog that inhibits DNA synthesis [1].

DNA synthesis is a natural creation of deoxyribonucleic acid (DNA) molecules and plays an important role in cell growth.

Fludarabine is a prodrug and is phosphorylated to the nucleoside triphosphate (F-ara-ATP) in cells to elicit biological activity. It affected a series of enzymes that required in DNA synthesis such as DNA primase, DNA polymerases, DNA ligase I, ribonucleotide reductase and 3’-5’ exonuclease activity of DNA polymerases δ and ε [1]. In human myeloma cell RPMI8226, fludarabine significantly inhibited cells growth and reduced phosphorylation of Akt. Also, it reduced XIAP and survivin, the inhibitors of apoptosis proteins (IAP) family [2]. Fludarabine can act as a cytosolic 50-nucleotidase II (cN-II) inhibitor [3].

In immunodeficient mice bearing RPMI8226 myeloma xenografts, fludarabine (40 mg/kg) slowed down the growth of tumors by about 5-fold in 25 d comparing with the control tumors [2].

参考文献:
[1].  Gandhi V, Huang P, Plunkett W. Fludarabine inhibits DNA replication: a rationale for its use in the treatment of acute leukemias. Leuk Lymphoma, 1994, 14 Suppl 2: 3-9.
[2].  Meng H, Yang C, Ni W, et al. Antitumor activity of fludarabine against human multiple myeloma in vitro and in vivo. Eur J Haematol, 2007, 79(6): 486-493.
[3].  Cividini F, Pesi R, Chaloin L, et al. The purine analog fludarabine acts as a cytosolic 5'-nucleotidase II inhibitor. Biochem Pharmacol, 2015, 94(2): 63-68.