Drug intelligence / Profile preview

fludarabine + cytarabine + cyclophosphamide

Development stage
Preclinical
Lead developer
Bayer
Modality
Classical Binding Small Molecules → Small Molecules, Covalent Small Molecules → Small Molecules, Nucleic Acid-Directed Small Molecules → Small Molecules
Administration
Intravenous
01

Overview

fludarabine + cytarabine + cyclophosphamide is a multi-agent chemotherapy combination used primarily in hematologic malignancies, most notably as part of intensive regimens for acute myeloid leukemia (AML) and related myeloid disorders. Fludarabine is a purine nucleoside analogue that, after intracellular phosphorylation, inhibits DNA polymerase, ribonucleotide reductase, and DNA primase, thereby blocking DNA synthesis and repair and inducing apoptosis in rapidly dividing lymphoid and myeloid cells. Cytarabine is a deoxycytidine analogue that is converted intracellularly to ara-CTP, which is incorporated into DNA and inhibits DNA polymerase, leading to chain termination and cell death; prior exposure to fludarabine enhances intracellular accumulation of ara-CTP and augments cytarabine cytotoxicity in AML blasts.[4] Cyclophosphamide is an alkylating agent that is metabolized to active phosphoramide mustard, which forms DNA crosslinks and strand breaks, further impairing DNA replication and triggering apoptosis. In combination, these agents provide synergistic antileukemic activity through complementary inhibition and damage of DNA synthesis pathways, but at the cost of profound myelosuppression and immunosuppression, and they are typically administered intravenously in specialized oncology settings.

02

Targets

DNAPOLA1 (DNA polymerase alpha)DNA-directed primase/polymerase protein (PrimPol)RNR (Ribonucleotide reductase)

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