Fludarabine是一种氟化嘌呤类似物，是一种核酸合成抑制剂和一种 STAT1 激活抑制剂。它抑制细胞因子诱导的正常静止或激活淋巴细胞中 STAT1 和 STAT1 依赖性基因转录的激活，有抗肿瘤活性。

Fludarabine is a nucleic acid synthesis Inhibitor and a STAT1 activation inhibitor.

Myeloma cell line RPMI8226 was efficiently inhibited by fludarabine, concomitantly with decreased phosphorylation of Akt, down-regulation of the inhibitor of apoptosis proteins (IAP) family. Fludarabine also induced cytotoxicity in dexamethasone-sensitive (MM.1S) and -resistant (MM.1R) cells at 48 h with IC50 of 13.48 μg/mL and 33.79 μg/mL, respectively [1]. Compared with control, fludarabine induced significant reduction of STAT-1 phosphorylation, whereas it did not change JAK2 activation. Also, fludarabine did not significantly affect the phosphorylation of ERK1/2 and Akt in cultured rat VSMCs [2]. The effect of fludarabine and mafosfamide was dose-dependent. Mafosfamide and fludarabine had a synergistic effect in inducing apoptosis of B-CLL cells. Mafosfamide significantly increased the apoptosis induced by fludarabine on CD19(+) cells, but not on CD3(+) cells [3].

RPMI8226 myeloma xenograft model was established using severe combined immunodeficient mice. The tumors treated with fludarabine at 40 mg/kg increased less than 5-fold in 25 d compared with approximately 10-fold in the control tumors [1]. Fourteen days after balloon injury, neointima formation was reduced by fludarabine treatment, and the inhibitory effect of fludarabine was directly related to the applied dose. The neointimal tissue of the injured carotid artery was reduced from ～30 to ～55% in the rats treated with the different doses of the drug, respectively, compared with the vehicle-treated rats [2].

VSMCs were isolated from the aorta of male Wistar rats weighing ～350–500 g, as previously described. For cell culture experiments, 2 × 10^5 rat VSMCs were plated in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS). Semiconfluent VSMCs were starved by incubation in 0.5% FBS/DMEM for 36–48 h and then serum-stimulated with normal growth medium (i.e., DMEM containing 10% FBS) in the presence or absence of fludarabine (50 μM) [2].

The animals in this study were handled according to the animal welfare regulation of the Magna Graecia University of Catanzaro, and the protocol was approved by the animal use committee of this institution. Fifty Wistar rats weighing 340 ± 40 g were anesthetized with an intramuscular injection of 100 mg/kg ketamine and 5 mg/kg xylazine. Angioplasty of the common carotid artery was performed using a balloon embolectomy catheter, as previously described and well validated in our laboratory. Fludarabine was dissolved in 30% pluronic F127 gel to the final concentrations of 2.5, 5, 15, or 25 mg/ml. At the time of balloon injury, gel containing fludarabine or vehicle was applied around the middle segment (2 cm in length) of the right injured carotid artery (0.1 ml per 1-cm length of the artery segment, equivalent to 0.5, 1, 3, or 5 mg of total fludarabine locally delivered), as previously described. As a control experiment, 200 μl of fludarabine/gel solution (25 mg/ml) were applied around the sham-operated carotid artery. To study the fludarabine toxicity, laboratory studies were performed at baseline and 2 wk after drug local delivery (25 mg/ml). Arterial pressure and heart rate were measured indirectly by a tail-cuff plethysmographic technique [2].

21679-14-1

C10H12FN5O4

285.235

氟达拉宾;F-ara-A;氟达拉滨;NSC 118218;Fludarabinum

DMSO:28.5 mg/mL (100 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years