Fazarabine

Fazarabine (Kymarabine; Ara-AC; NSC 281272) is an orally active, blood-brain barrier permeable DNA polymerase inhibitor and antitumor agent. Fazarabine interferes with DNA synthesis via intracellular activation into a triphosphate nucleotide that directly incorporates into DNA, inducing cytotoxicity, myelosuppression, as well as moderate nausea and vomiting. Fazarabine is resistant to deamination by cytidine-deoxycytidine deaminase and undergoes spontaneous aqueous degradation. Fazarabine exerts time-dependent, broad-spectrum activity against leukemia and solid tumors. Fazarabine can be used in research related to refractory malignancies, acute leukemia, and blast-phase chronic myeloid leukemia^[1][2]. In Vitro:Fazarabine (0.1-1 μM; 24 h) reduces the clonogenic survival rate of the human T-lymphoblastic leukemia cell line Molt-4: after 24 h of exposure, the inhibition rate reaches 50% at 0.1 μM and 98% at 1 μM^[1].
Fazarabine exhibits broad-spectrum antitumor activity against the P388 and L1210 cell lines^[2]. In Vivo:Fazarabine (administered every 3 hours; dosed on days 1, 5, and 9; once daily; maximum treatment duration of 9 days) exhibits in vivo antileukemic activity against mouse L1210 and P388 leukemia^[1].