Cellular DNA and RNA (DNA/RNA)

Cellular DNA and RNA serve as the primary molecular targets for the antimetabolite drug fludarabine. Fludarabine, a purine analog, is converted intracellularly into its active metabolite, fludarabine triphosphate (F-ara-ATP), which competes with deoxyadenosine triphosphate (dATP) for incorporation into nascent DNA strands during replication and repair (PubChem, 2024). Once incorporated, the presence of the arabinose sugar moiety causes steric hindrance, leading to DNA chain termination and the inhibition of DNA polymerases alpha, delta, and epsilon (StatPearls, 2023). Beyond DNA, fludarabine is also incorporated into RNA, where it interferes with RNA processing, splicing, and the translation of essential proteins (PubMed, 2023). These cumulative disruptions to nucleic acid integrity and function trigger programmed cell death (apoptosis), particularly in quiescent and proliferating lymphocytes, which underlies its efficacy in treating chronic lymphocytic leukemia and indolent lymphomas (NIH, 2024).

Other names

Genomic DNACellular RNANucleic acidsNuclear DNASubstrate for nucleoside analogs

Incorporation of the active triphosphate metabolite into DNA and RNA strands, leading to chain termination, inhibition of DNA polymerases, and interference with DNA repair and RNA processing.