| 名稱 | Fludarabine |
| 描述 | Fludarabine (Fludarabinum) is a fluorinated purine analog, an inhibitor of nucleic acid synthesis and an inhibitor of STAT1 activation. Fludarabine has antitumor activity and can be used for the treatment of leukemia and lymphoma. |
| 細(xì)胞實(shí)驗(yàn) | 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]. |
| 動物實(shí)驗(yàn) | 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]. |
| 體外活性 | 方法：多發(fā)性骨髓瘤細(xì)胞 RPMI8226、MM.1S 和 MM.1R 用 Fludarabine (0-64 μg/mL) 處理 24-48 h，使用 MTT Assay 檢測細(xì)胞活力。
結(jié)果：Fludarabine 劑量-時(shí)問依賴性抑制 RPMI8226 細(xì)胞增殖，24 h 的 IC50 為 1.54 μg/mL。48 h，F(xiàn)ludarabine 對MM.1S 和 MM.1R 細(xì)胞的 IC50 分別為 13.48 μg/mL 和 33.79 μg/mL。[1]
方法：大鼠主動脈 VSMCs 用 Fludarabine (50 μM) 和 FBS 處理 30 min，使用 Western Blot 檢測靶點(diǎn)蛋白表達(dá)水平.
結(jié)果：FBS 刺激產(chǎn)生了漸進(jìn)的 JAK2 和 STAT-1 激活，F(xiàn)ludarabine 誘導(dǎo) STAT-1 磷酸化的顯著減少，而它沒有改變 JAK2 的激活。[2] |
| 體內(nèi)活性 | 方法：為檢測體內(nèi)抗腫瘤活性，將 Fludarabine (8-40 mg/kg) 腹腔注射給攜帶多發(fā)性骨髓瘤 RPMI8226 的 SCID 小鼠，每天一次，持續(xù)三天。
結(jié)果：與對照腫瘤中的約 10 倍相比，用 40mg/kg 的 Fludarabine 治療的腫瘤在 25 天內(nèi)增加了不到 5 倍，證明了 Fludarabine 在體內(nèi)的抗腫瘤活性。[1]
方法：為研究對移植物抗宿主病 (GVHD) 的作用，將 Fludarabine (0.8 mg/kg) 腹腔注射給攜帶 B 細(xì)胞白血病 (BCL-1) 的 (BALB/c x C57BL/6)F1 小鼠，每兩周接受兩個周期的給藥五天，然后腹腔注射 cyclophosphamide (400 mg/kg)。
結(jié)果：在移植前用含 Fludarabine 的方案治療的小鼠在臨床和尸檢中的 GVHD 也少得多，而移植物抗白血病似乎在相同的動物中增加。[3] |
| 存儲條件 | Store at low temperature,Keep away from direct sunlight,Keep away from moisture
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | DMSO : 240 mg/mL (841.43 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 2.86 mg/mL (10.03 mM), Solution.
|
| 關(guān)鍵字 | STAT1 | STAT | RNASynthesis | RNA Synthesis | purine analogue | NucleosideAntimetabolite | Nucleoside Antimetabolite/Analog | Nucleoside Antimetabolite | NSC-118218 | NSC118218 | lymphoproliferative malignancies | Inhibitor | inhibit | fluorinated | Fludarabine | DNASynthesis | DNA/RNA Synthesis | DNA synthesis | Apoptosis | Analog |
| 相關(guān)產(chǎn)品 | Formamide | Urea | Guanidine hydrochloride | Dimethyl phthalate | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Sildenafil citrate | Stavudine | Tamoxifen | Thymidine |
| 相關(guān)庫 | 抑制劑庫 | 抗癌活性化合物庫 | 經(jīng)典已知活性庫 | 抗癌上市藥物庫 | 已知活性化合物庫 | 臨床失敗化合物庫 | 抗衰老化合物庫 | FDA 上市藥物庫 | 免疫/炎癥分子化合物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |