Etoposide phosphate
(Synonyms: 磷酸依托泊苷; BMY-40481) 目录号 : GC60826
Etoposidephosphate(BMY-40481)是一种有效的抗癌(anti-cancer)化疗试剂和一种选择性拓扑异构酶II(topoisomeraseII)抑制剂，可以防止DNA链的重新连接。Etoposidephosphate是依托泊苷的磷酸酯前药，被认为与Etoposide活性相当。Etoposidephosphate诱导细胞周期阻滞、凋亡(apoptosis)和自噬(autophagy)。
Cas No.:117091-64-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
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- SDS (Safety Data Sheet)
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Etoposide phosphate (BMY-40481) is a potent anti-cancer chemotherapy agent and a selective topoisomerase II inhibitor to prevent re-ligation of DNA strands. Etoposide phosphate is the phosphate ester prodrug of etoposide and is considered as active equivalent to Etoposide. Etoposide phosphate induces cell cycle arrest, apoptosis, and autophagy[1][2].
Etoposide phosphate is a water-soluble derivative and probable prodrug of etoposide characterized by the presence of a phosphate group in position 4' of the E ring of the etoposide molecule[1].Etoposide phosphate (0-1 μM; 72 hours) inhibits HCT116 FBXW+/+, FBXW-/- and p53-/- as a dose-dependent manner, exhibits IC50 values of 0.945 μM; 0.375 μM; and 1.437 μM, respectively[2].Etoposide phosphate (25 μM; 6 hours) delays p53 recover in FBXW7-deficient cells. In addition, FBXW7 expression is disappeared in FBXW7-/- cells[2]. Cell Viability Assay[2] Cell Line: FBXW+/+, FBXW-/- and p53-/- cell
Etoposide phosphate (intravenous injection; 50, 100, or 150 mg/kg; single dose) has clinical symptomology of progressive ataxia, impaired righting reflex, and splaying and paresis of fore- and hindlimbs at day 8 in female CD-1 mice[3]. Animal Model: Female CD-1 mice[3]
[1]. Witterland AH, et al. Etoposide phosphate, the water soluble prodrug of etoposide. Pharm World Sci. 1996 Oct;18(5):163-70. [2]. Cui D, et al. FBXW7 Confers Radiation Survival by Targeting p53 for Degradation.Cell Rep. 2020 Jan 14;30(2):497-509.e4. [3]. Bregman CL, et al. Etoposide- and BMY-40481-induced sensory neuropathy in mice.Toxicol Pathol. 1994 Sep-Oct;22(5):528-35. [4]. SUMMARY OF PRODUCT CHARACTERISTICS
| Cas No. | 117091-64-2 | SDF | |
| 别名 | 磷酸依托泊苷; BMY-40481 | ||
| Canonical SMILES | O=C1OC[C@]2([H])[C@H](O[C@H]3[C@@H]([C@H]([C@@H]([C@@H](CO4)O3)O[C@@H]4C)O)O)C5=C(C=C6OCOC6=C5)[C@@H](C7=CC(OC)=C(OP(O)(O)=O)C(OC)=C7)[C@]21[H] | ||
| 分子式 | C29H33O16P | 分子量 | 668.54 |
| 溶解度 | Water: 125 mg/mL (186.97 mM) | 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 | 1.4958 mL | 7.479 mL | 14.958 mL |
| 5 mM | 0.2992 mL | 1.4958 mL | 2.9916 mL |
| 10 mM | 0.1496 mL | 0.7479 mL | 1.4958 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。
Etoposide phosphate: what, why, where, and how?
Semin Oncol 1996 Dec;23(6 Suppl 13):1-7.PMID:8996569doi
The podophyllotoxin derivatives etoposide and teniposide are active in the treatment of a variety of malignant conditions. Both represent chemical modifications of podophyllin, an extract of Podophyllum peltatum (May apple, mandrake, Indian apple, wild lemon, or duck's foot), a plant long used as a folk remedy and recognized in the 19th century to be effective in the treatment of cancer. While etoposide is active in the treatment of many cancers and is widely used, it has a number of limitations due to its lack of water solubility. Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is rapidly and completely converted to the parent compound after intravenous dosing. The pharmacokinetic profile of etoposide after treatment with either etoposide or Etoposide phosphate is identical. Toxicity and clinical activity also are the same. Because Etoposide phosphate is water soluble and can be made up to a concentration of 20 mg/mL, however, it can be given as a 5-minute bolus, in high doses in small volumes, and as a continuous infusion. Furthermore, it is not formulated with polyethylene glycol, polysorbate 80 (Tween; ICI Americas, Wilmington, DE), and ethanol, and does not cause acidosis when given at high doses. The easier-to-use Etoposide phosphate represents an improved formulation of etoposide.
Immediate severe hypersensitivity reaction to Etoposide phosphate: Case report and review of the literature
J Oncol Pharm Pract 2022 Jun;28(4):1019-1023.PMID:35037804DOI:10.1177/10781552211073345.
Introduction: Hypersensitivity reactions from intravenous (IV) etoposide have been rarely reported, with these being seen more commonly with etoposide than with Etoposide phosphate. This is generally explained by the need for polysorbate 80, a known cause of hypersensitivity, as a solubiliser, in the etoposide formulation. Case report: We report a 22-year-old male, being treated with adjuvant BEP (bleomycin/Etoposide phosphate/cisplatin) for a testicular germ cell tumour. Bleomycin and cisplatin were administered without incident. Within one minute of Etoposide phosphate commencement he experienced a severe hypersensitivity reaction, consisting of widespread erythematous rash, facial swelling, and nausea. Observations included unrecordable blood pressure, tachycardia, hypoxia, and loss of consciousness, confirming a diagnosis of anaphylactic shock. Management and outcome: Etoposide phosphate was ceased immediately. He was successfully managed with IV hydrocortisone, IV promethazine, intramuscular adrenaline, IV fluids and oxygen. Following admission for observation, significant improvement occurred over 48 h. Discussion: Hypersensitivity reactions to etoposide were first reported in the 1980s. Following reactions to etoposide, substituting Etoposide phosphate into chemotherapy regimens has commonly allowed treatment to continue without incidence. Anaphylactic reactions to Etoposide phosphate were first documented in 2012, with further cases reported subsequently. Unlike etoposide, Etoposide phosphate is highly soluble in aqueous solutions and doesn't require adjuvants in the formulation. Hypersensitivity reactions to Etoposide phosphate are therefore likely related to the etoposide drug molecule itself. Clinicians should be aware of this rare, but potentially life-threatening, toxicity when using etoposide-based treatments and have procedures in place to urgently manage any hypersensitivity reactions that may occur.
Etoposide phosphate, the water soluble prodrug of etoposide
Pharm World Sci 1996 Oct;18(5):163-70.PMID:8933576DOI:10.1007/BF00820727.
Etoposide (Vepesid) is a widely used drug in a variety of neoplasms. To improve the pharmaceutical characteristics of etoposide, Etoposide phosphate (Etopophos, Bristol-Myers Squibb) has been developed as a prodrug. Etoposide phosphate is the phosphate ester derivative of etoposide. In comparison to the parent compound, Etoposide phosphate is highly soluble in water and can be readily formulated for intravenous use, resulting in higher clinical application. This paper presents information on the pharmaceutical properties and the current status of Etoposide phosphate in clinical trials.
Etoposide and Etoposide phosphate hypersensitivity in children: Incidence, risk factors, and prevention strategies
J Oncol Pharm Pract 2020 Mar;26(2):397-405.PMID:31315549DOI:10.1177/1078155219858390.
Introduction: Etoposide is critical in treating pediatric cancers, although hypersensitivity can be severe and treatment-limiting. Reported rates of hypersensitivity range from 2% to 51%. Hypersensitivity data for Etoposide phosphate, a newer product, are lacking. The primary objective of this study was to assess etoposide and Etoposide phosphate hypersensitivity incidence. Secondary objectives included evaluation of potential risk factors for hypersensitivity and strategies to prevent recurrence. Methods: This retrospective cohort study evaluated pediatric patients who received initial Etoposide phosphate or etoposide dose between August 2012 and July 2017. The primary outcome was documentation of hypersensitivity within four months of initial dose. Potential risk factors evaluated included age, allergies, dose, infusion rate, infusion concentration, and premedication. Results: Of 246 patients, hypersensitivity reactions occurred in five of 54 patients (9.3%) who received Etoposide phosphate and 52 of 192 patients (27.1%) who received etoposide (p = 0.0061). For etoposide, the mean initial infusion rate was 64.6 ± 40.9 mg/m2/h for patients with hypersensitivity and 49.5 ± 33.4 mg/m2/h without hypersensitivity (p = 0.0886). Etoposide phosphate rate was not associated with hypersensitivity. Recurrent hypersensitivity occurred in one of nine patients (11.1%) who received etoposide desensitization and one of 38 patients (2.6%) who changed formulation to Etoposide phosphate. Conclusions: Etoposide was associated with more hypersensitivity than Etoposide phosphate in pediatric patients. Etoposide hypersensitivity was associated with higher infusion rates, but not Etoposide phosphate. Differences in hypersensitivity incidence and infusion rate influence indicate a formulation-effect. Etoposide hypersensitivity recurrence may be prevented by changing to Etoposide phosphate formulation. During Etoposide phosphate shortages, etoposide desensitization may prevent recurrent hypersensitivity.
Early studies of Etoposide phosphate, a water-soluble prodrug
Semin Oncol 1996 Dec;23(6 Suppl 13):8-14.PMID:8996570doi
Etoposide phosphate (Etopophos; Bristol-Myers Squibb Company, Princeton, NJ) is a water-soluble prodrug of etoposide that is converted in vivo by endogenous phosphatases to the active drug etoposide. This conversion process is efficient and not saturable in humans at doses between 50 and 1,600 mg/m2. The resultant etoposide demonstrates classic pharmacokinetics, and the etoposide phosphates dose is linearly related to peak levels and the area under the concentration-time curve of etoposide. The absence of noxious solvents and the ability to administer the drug in small volumes over short periods make etoposide a phosphate attractive for conventional- and high-dose clinical programs.