Drug intelligence / Profile preview

fludarabine + pegylated liposomal doxorubicin

Development stage
Preclinical
Lead developer
Johnson & Johnson
Modality
Nanoparticles → Drug Delivery Systems, Small Molecules
Administration
Intravenous
01

Overview

This is a combination chemotherapy regimen consisting of fludarabine, a purine analog antimetabolite, and pegylated liposomal doxorubicin, an anthracycline antibiotic formulated in long-circulating PEG-coated liposomes. Fludarabine inhibits DNA synthesis by interfering with DNA polymerase alpha, ribonucleotide reductase, and DNA primase activities, leading to inhibition of cancer cell proliferation[3][4]. Pegylated liposomal doxorubicin intercalates into DNA and inhibits topoisomerase II activity, resulting in cytotoxicity through the generation of free radicals and induction of apoptosis. The pegylation extends circulation time and alters tissue distribution compared to conventional doxorubicin. This combination is primarily investigated for hematologic malignancies such as chronic lymphocytic leukemia (CLL), leveraging the synergistic cytotoxic effects on malignant lymphocytes[1].

Other names
fludarabine and pegylated liposomal doxorubicinfludarabine plus pegylated liposomal doxorubicin
02

Targets

TOP2A (DNA topoisomerase II)DNA-directed primase/polymerase protein (PrimPol)POLA1 (DNA polymerase alpha)RNR (Ribonucleotide reductase)

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