Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium
(Synonyms: CA 4DP; CA 4P; Combretastatin A4 disodium phosphate) 目录号 : GC12308
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium是一种微管解聚药物，作为Combretastatin A4(CA4)的水溶性前体药物。
Cas No.:168555-66-6
Sample solution is provided at 25 µL, 10mM.
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Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium is a microtubule destabilizing drug, a water-soluble prodrug of combretasain A4(CA4) [1]. Fosbretabulin Disodium can be dephosphorylated in the body to form the active metabolite CA4, which promotes microtubule polymerization and thereby induces G2/M phase cell cycle arrest[2]. Fosbretabulin Disodium has been widely used to induce tumor necrosis and is employed as an adjuvant to develop new combined therapies[3].
In vitro, Fosbretabulin Disodium treatment for 48 hours significantly inhibited the proliferation of HepG2, Bel-7402, and MCF-7 cells, with IC50 values of 0.002μM, 0.04μM, and 0.011μM, respectively[4]. Fosbretabulin Disodium treatment at 1µM for 30min disrupted the microtubule skeleton of human umbilical vein endothelial cells (HUVECs) and altered cell morphology[5].
In vivo, Fosbretabulin Disodium treatment, administered by tail vein bolus (60mg/10ml/kg; 24h interval; four doses), resulted in multifocal necrosis, inflammatory cell infiltration, and telangiectasia in the myocardium of rats [6]. A single intraperitoneal injection of Fosbretabulin Disodium at a dose of 100mg/kg for 30min resulted in a rapid decrease in tumor perfusion followed by a subsequent decrease in interstitial fluid pressure in the C3H breast cancer mouse model[7]. A single intravenous injection of Fosbretabulin Disodium (10mg/kg) combined with low-dose γ-ray irradiation (0.20Gy; 0.685rad/sec) treatment for 24h inhibited N-nitrosodiethylamine (NDEA)-induced hepatocellular carcinoma development in rats by down-regulating CD31 expression and gene expression of ROCK1 and VEGF[8].
References:
[1] Smolarczyk R, Czapla J, Jarosz-Biej M, et al. Vascular disrupting agents in cancer therapy[J]. European journal of pharmacology, 2021, 891: 173692.
[2] Lu Y, Chen J, Xiao M, et al. An overview of tubulin inhibitors that interact with the colchicine binding site[J]. Pharmaceutical research, 2012, 29(11): 2943-2971.
[3] Nagaiah G, Remick S C. Combretastatin A4 phosphate: a novel vascular disrupting agent[J]. Future Oncology, 2010, 6(8): 1219-1228.
[4] Liu Y, Wu Y, Gu Y, et al. Synthesis and structure-activity relationship study of water-soluble carbazole sulfonamide derivatives as new anticancer agents[J]. European journal of medicinal chemistry, 2020, 191: 112181.
[5] Kanthou C, Tozer G M. The tumor vascular targeting agent combretastatin A–4-phosphate induces reorganization of the actin cytoskeleton and early membrane blebbing in human endothelial cells[J]. Blood, The Journal of the American Society of Hematology, 2002, 99(6): 2060-2069.
[6] Tochinai R, Nagata Y, Ando M, et al. Combretastatin A4 disodium phosphate-induced myocardial injury[J]. Journal of toxicologic pathology, 2016, 29(3): 163-171.
[7] Ley C D, Horsman M R, Kristjansen P E G. Early effects of combretastatin-A4 disodium phosphate on tumor perfusion and interstitial fluid pressure[J]. Neoplasia, 2007, 9(2): 108-112.
[8] Alghzzawy Z M, Elmaghraby T K, El-Hamid Hagag S A, et al. Combretastatin A-4 disodium phosphate and low dose gamma irradiation suppress hepatocellular carcinoma by downregulating ROCK1 and VEGF gene expression[J]. Molecular biology reports, 2020, 47(3): 1883-1893.
Fosbretabulin (Combretastatin A4 Phosphate (CA4P)) Disodium是一种微管解聚药物，作为Combretastatin A4(CA4)的水溶性前体药物[1]。Fosbretabulin Disodium在体内经去磷酸化后可形成活性代谢物CA4，通过促进微管蛋白聚合诱导G2/M期细胞周期阻滞[2]。Fosbretabulin Disodium目前已广泛应用于诱导肿瘤坏死，并作为辅助物用于开发新型联合疗法[3]。
在体外，Fosbretabulin Disodium处理48小时能显著抑制HepG2、Bel-7402和MCF-7细胞增殖，IC50值分别为0.002μM、0.04μM和0.011 μM[4]。使用1µM的Fosbretabulin Disodium处理人脐静脉内皮细胞(HUVECs) 30分钟，可破坏微管骨架结构并改变细胞形态[5]。
在体内，通过尾静脉推注Fosbretabulin Disodium（60mg/10ml/kg; 24小时间隔给药; 给药4次）可导致大鼠心肌出现多灶性坏死、炎性细胞浸润及毛细血管扩张[6]。单次腹腔注射100mg/kg剂量的Fosbretabulin Disodium 30分钟，能迅速降低C3H乳腺癌小鼠模型的肿瘤灌注量，并随之降低组织间液压力[7]。单次静脉注射Fosbretabulin Disodium（10mg/kg）联合低剂量γ射线（0.20Gy; 0.685rad/sec）照射处理24小时，可通过下调CD31表达及ROCK1、VEGF基因表达，抑制N-nitrosodiethylamine (NDEA)诱导的大鼠肝细胞癌进展[8]。
| Cell experiment [1]: | |
Cell lines | MCF-7 cells |
Preparation Method | MCF-7 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum, 100units /ml penicillin and 100μg/ml streptomycin at 37℃, 5% CO2, and high humidity. Cells were seeded in standard 96-well microplates at a density of approximately 5×105 cells/well and cultured for 24h to allow adherence. Cells were incubated with different concentrations of Fosbretabulin Disodium (0.0001, 0.001, 0.01, 0.1, 1.0, and 10µM) for 48 hours. Cells were fixed at the bottom of each well with ice-cold 50% trichloroacetic acid (TCA) and incubated for 2h at 4°C. After washing and drying, the cells were stained with 70μl of 0.4% (w/v) SRB for 10min (room temperature), washed five more times with 1% acetic acid, and air dried. The bound dye was dissolved with 100μl of 10mM Tris base solution, and the optical density values were determined at 515nm. |
Reaction Conditions | 0.0001, 0.001, 0.01, 0.1, 1.0, and 10µM; 48h |
Applications | Fosbretabulin Disodium treatment inhibited the cell viability of MCF-7 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male Wistar albino rats |
Preparation Method | Male Wistar albino rats weighing 140 to 160g were maintained under standard conditions and had ad libitum access to fresh water and feed. A total of 126 rats were randomly divided into 7 groups (n=18). (I) normal control group: rats were given normal saline orally during the experiment. (II) Fosbretabulin Disodium group; Normal rats received Fosbretabulin Disodium (10mg/kg) intravenously. (III) LDR group: normal rats were exposed to a single low dose of γ-rays (0.20Gy; 0.685rad/s). (IV) NDEA/HCC group: rats were treated with NDEA (20mg/kg; 5 times a week for 8 weeks) followed by NDEA (10mg/kg, 5 times a week for 9 weeks) to induce hepatocellular carcinoma (HCC). (V) NDEA/HCC+LDR group: rats were treated with NDEA followed by low-dose γ-ray irradiation (0.20Gy; 0.685rad/s). (VI) NDEA/HCC+Fosbretabulin Disodium: rats were treated with NDEA followed by intravenous injection of Fosbretabulin Disodium (10mg/kg). All groups were sacrificed 24 hours after treatment, and rat livers were collected for analysis. |
Dosage form | 10mg/kg for once; i.v. |
Applications | Fosbretabulin Disodium treatment combined with low-dose γ-ray irradiation repressed the expression of CD31 and gene expression of ROCK1 and VEGF in rats. |
References: | |
| Cas No. | 168555-66-6 | SDF | |
| 别名 | CA 4DP; CA 4P; Combretastatin A4 disodium phosphate | ||
| 化学名 | disodium;[2-methoxy-5-[(Z)-2-(3,4,5-trimethoxyphenyl)ethenyl]phenyl] phosphate | ||
| Canonical SMILES | COC1=C(C=C(C=C1)C=CC2=CC(=C(C(=C2)OC)OC)OC)OP(=O)([O-])[O-].[Na+].[Na+] | ||
| 分子式 | C18H19Na2O8P | 分子量 | 440.29 |
| 溶解度 | ≥ 11.7mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2712 mL | 11.3562 mL | 22.7123 mL |
| 5 mM | 454.2 μL | 2.2712 mL | 4.5425 mL |
| 10 mM | 227.1 μL | 1.1356 mL | 2.2712 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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- Purity: >99.00%
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