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Purity: ≥98%
Etoposide phosphate (BMY40481) is the phosphate salt of Etoposide (known as VP-16 and VP-16213), which is a chemotherapeutic drug used for the treatments of various cancers and is a semisynthetic derivative of podophyllotoxin which inhibits DNA synthesis via topoisomerase II inhibitory activity. Etoposide is extracted from the mandrake root Podophyllum peltatum. It possesses potent antineoplastic properties, and binds to and inhibits topoisomerase II. Etoposide works by ligating cleaved DNA molecules, resulting in the accumulation of single- or double-strand DNA breaks, the inhibition of DNA replication and transcription, and apoptotic cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. 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.
| Targets |
Topoisomerase II
|
|---|---|
| ln Vitro |
Etoposide phosphate is the solubility of etoposide and could be its prodrug; etoposide is identified by the presence of a phosphate group at the 4' position of its E ring [1]. The inhibitory effects of etoposide phosphate (0-1) on HCT116 FBXW+/+, FBXW-/-, and p53-/- are dose-dependent and have IC50 values of 0.945 μM, 0.375 µM, and 1.437 µM[2]. 6 hours) postpones the recovery of p53 in cells lacking FBXW7. Moreover, in FBXW7-/-cells, FBXW7 expression vanished [2].
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| ln Vivo |
In female CD-1 mice, a single dosage of mortgage phosphate (IV; 50, 100, or 150 mg/kg) results in gradual analgesic rescue, righting crises, torsional limb splay, and paralysis.
On day 8, female CD-1 mice administered with etoposide phosphate (50, 100, or 150 mg/kg in a single dosage) exhibit increasing ataxia, decreased righting reflex, and splaying and paresis of the fore- and hindlimbs[3].
The effects of high toxic doses of the anticancer drugs, etoposide and its phosphate derivative, BMY-40481, on the nervous system of female CD-1 mice were examined by light microscopy (LM) and transmission electron microscopy. Mice were euthanatized 4 wk following a single iv injection of either 0, 50, 100, or 150 mg/kg of BMY-40481 or 44 or 88 mg/kg of etoposide. Mice treated with 100 or 150 mg/kg of BMY-40481 or 88 mg/kg of etoposide had clinical symptomology of progressive ataxia, impaired righting reflex, and splaying and paresis of fore- and hindlimbs at day 8. Similar, dose-related LM changes were observed with both drugs at all doses and consisted of degeneration of dorsal root ganglion cells and axonal degeneration of their distal and proximal processes in peripheral nerves, dorsal spinal roots, and dorsal funiculi of spinal cord. Axonal degeneration was characterized by LM as shrinkage, swelling, and fragmentation of axon cylinders accompanied by secondary demyelination. Degenerative changes in ganglion cell bodies included eccentric nuclei, cytoplasmic vacuolation, central chromatolysis, and peripheral clumping of Nissl's bodies. Ultrastructurally, ganglion cell bodies had focally extensive dilation of the rough endoplasmic reticulum, mitochondrial swelling, increased numbers of phagolysosomes and prominent aggregations of microfilaments (globular filamentous bodies). Ultrastructural axonal changes occurred primarily in large, myelinated fibers and consisted of axonal swelling or loss, thinning of myelin sheaths, and a decrease in the number of organelles. This is the first report of etoposide-related sensory neuropathy in laboratory rats, a model that my be useful for the study of etoposide-related peripheral neuropathy in humans.[3] |
| Cell Assay |
Cell viability test[2]
Cell Types: FBXW+/+, FBXW-/- and p53-/- Cell Tested Concentrations: 0.025 μM, 0.05 μM, 0.075 μM, 0.1 μM, 0.2 μM, 0.4 μM, 0.6 μM, 0.8 μM, 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Inhibition of HCT116 FBXW+/+, FBXW-/- and p53-/- cell growth in concentrated form. Western Blot Analysis[2] Cell Types: HCT116 FBXW7+/+ or FBXW7-/- Cell Tested Concentrations: 25 μM Incubation Duration: 6 hrs (hours) Experimental Results: It shows that the recovery of p53 levels after DNA damage is mediated by FBXW7. |
| Animal Protocol |
Animal/Disease Models: Female CD-1 mice[3]
Doses: 50, 100 or 150 mg/kg Route of Administration: intravenous (iv) (iv)injection; clinical symptoms[3]. Single dose Experimental Results: Under light microscopy (LM), degeneration of dorsal root ganglion cells in peripheral nerves, dorsal roots and dorsal cord of the spinal cord and axonal degeneration of their distal and proximal processes were observed at all doses. |
| References |
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| Additional Infomation |
Etoposide phosphate is a furonaphthodioxole.
Etoposide Phosphate is a phosphate salt of a semisynthetic derivative of podophyllotoxin. Etoposide binds to the enzyme topoisomerase II, inducing double-strand DNA breaks, inhibiting DNA repair, and resulting in decreased DNA synthesis and tumor cell proliferation. Cells in the S and G2 phases of the cell cycle are most sensitive to this agent. (NCI04) See also: Etoposide (has active moiety). |
| Molecular Formula |
C29H33O16P
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|---|---|
| Molecular Weight |
668.53652
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| Exact Mass |
666.136
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| Elemental Analysis |
C, 52.10; H, 4.98; O, 38.29; P, 4.63
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| CAS # |
117091-64-2
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| Related CAS # |
Etoposide;33419-42-0;Etoposide phosphate disodium;122405-33-8
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| PubChem CID |
6918092
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| Appearance |
White to off-white solid powder
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| Density |
1.55 g/cm3
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| Boiling Point |
907.7±75.0 °C at 760 mmHg
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| Flash Point |
502.7±37.1 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| LogP |
-1.28
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
46
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| Complexity |
1140
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| Defined Atom Stereocenter Count |
10
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| SMILES |
C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@H]3[C@H]4COC(=O)[C@@H]4[C@@H](C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)OP(=O)(O)O)OC)O)O
|
| InChi Key |
LIQODXNTTZAGID-OCBXBXKTSA-N
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| InChi Code |
InChI=1S/C29H33O16P/c1-11-38-9-20-27(42-11)23(30)24(31)29(43-20)44-25-14-7-17-16(40-10-41-17)6-13(14)21(22-15(25)8-39-28(22)32)12-4-18(36-2)26(19(5-12)37-3)45-46(33,34)35/h4-7,11,15,20-25,27,29-31H,8-10H2,1-3H3,(H2,33,34,35)/t11-,15+,20-,21-,22+,23-,24-,25-,27-,29+/m1/s1
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| Chemical Name |
[4-[(5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-8-oxo-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f][1,3]benzodioxol-9-yl]-2,6-dimethoxyphenyl] dihydrogen phosphate
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| Synonyms |
Etopofos; Etophos; Etopophos; Vepeside; Etopophos Preservative Free; BMY 40481;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4958 mL | 7.4790 mL | 14.9580 mL | |
| 5 mM | 0.2992 mL | 1.4958 mL | 2.9916 mL | |
| 10 mM | 0.1496 mL | 0.7479 mL | 1.4958 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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