Fludarabine
DNA synthesis inhibitor / A synthetic adenosine analog that inhibits DNA biosynthesis and is a clinically useful antineoplastic agent.1 In cells fludarabine accumulates as its 5’-triphosphate (F-ara-ATP) for which the rate-limiting step in formation is the conversion of fludarabine to its monophosphate.2 F-ara-ATP has multiple mechanisms of action including inhibition of ribonucleotide reductase, DNA polymerase, ligase and primase.2 A frequently used agent in myeloablative conditioning regimens for allogeneic hematopoietic cell transplantation.3 Immunosuppressive effects are mediated via inhibition of TNFα-stimulated production of IL-2 and IFN- through inactivation of NFB.4 Antagonist at adenosine A1 receptors.5
Biochemicals & reagents
21679-14-1
F-ara-A; NSC118218
1) Ross et al. (1993), Fludarabine. A review of its pharmacological properties and therapeutic potential in malignancy; Drugs, 45 737 2) Gandhi and Plunkett (2002), Cellular and clinical pharmacology of fludarabine; Pharmacokinet., 41 93 3) Langenhorst et al. (2019), Fludarabine exposure in the conditioning prior ro allogeneic hematopoietic cell transplantation predicts outcomes; Blood Adv., 3 2179 4) Nishioka et al. (2008), Fludarabine induces growth arrest and apoptosis of cytokine- or alloantigen-stimulated peripheral blood mononuclear cells and decreases production of Th1 cytokines via inhibition of nuclear factor kappaB; Bone Marrow Transplant., 41 303 5) Jensen et al. (2012), Cytotoxic purine nucleoside analogues bind to A1, A2A and A3 adenosine receptors; Naunyn Schmiedebergs Arch. Pharmacol., 385 519
-20°C
TARGET: GPCR; DNA -- PATHWAY: MAPK; NFkappaB; TNF; DNA synthesis -- RESEARCH AREA: Immunology -- DISEASE AREA: Cancer; Inflammation