Fazarabine, 法扎拉濱

Fazarabine is an orally-active pyrimidine analogue of an aza-substituted cytidine in which the ribose moiety is replaced by an arabinose sugar. Similar in action to cytarabine, fazarabine is phosphorylated by deoxycytidine kinase to a triphosphate form which competes with thymidine for incorporation into DNA; its incorporation into DNA inhibits DNA synthesis, resulting in tumor cell death and tumor necrosis. The presence of deoxycytidine kinase in a tumor is a determinant of tumor sensitivity to this drug. (NCI04)

Fazarabine is an N-glycosyl-1,3,5-triazine that is 4-amino-1,3,5-triazin-2(1H)-one substituted by a beta-D-arabinofuranosyl residue via an N-glycosidic linkage. A synthetic analogue of cytosine arabinoside and 5-azacytidine that incorporates structural features of both compounds, it shows good activity against a variety of transplanted tumors. It has a role as an antineoplastic agent. It is a N-glycosyl-1,3,5-triazine and a nucleoside analogue. It derives from a beta-D-arabinofuranose.

Fazarabine is a nucleoside analog that has been shown to be a potent inhibitor of the enzyme fyn tyrosine kinase and to have cytotoxic effects on human leukemia HL-60 cells. The chemical stability of fazarabine has been demonstrated in methyltransferase inhibition studies. Fazarabine is also an anti-cancer compound with selective toxicity towards colorectal adenocarcinoma cells. Fazarabine inhibits cell proliferation by inhibiting protein synthesis, which may be due to its ability to act as a DNA template, or its receptor activity. Fazarabine also has immunosuppressive properties and can be used for the treatment of autoimmune diseases such as rheumatoid arthritis, Crohn's disease, and psoriasis.