Etoposide 4 -Phosphate, Free Acid **
產(chǎn)品名稱：Etoposide 4'-Phosphate, Free Acid
產(chǎn)品貨號(hào)：LC E-4444
產(chǎn)品規(guī)格：100 MG
Etoposide 4'-phosphate is a water-soluble prodrug of etoposide that is rapidly and completely converted to etoposide, the active parent compound, after intravenous dosing. Unphosphorylated etoposide is active in the treatment of many cancers but its use is limited by its lack of water solubility. Etoposide is formulated with polyethylene glycol, polysorbate 80, and ethanol, but causes acidosis when given at high doses. Etoposide and etoposide 4'-phosphate have essentailly identical pharmacokinetic profiles, toxicity, and clinical activity. Schacter, L. "Etoposide phosphate: what, why, where, and how?" Semin. Oncol. 23: 1-7 (1996).
We also offer the unphosphorylated form of etoposide -- please see Cat. No. E-4488, Etoposide.
The conversion of etoposide 4'-phosphate to etoposide occurs in the GI tract after oral administration. de Jong, R.S., et al. "Conversion of the prodrug etoposide phosphate to etoposide in gastric juice and bile." Br. J. Cancer 76: 1480-1483 (1997).
Free etoposide inhibits topoisomerase II. A ternary complex of etoposide, DNA and the topoisomerase II enzyme forms and prevents re-ligation of the DNA strands. This results in errors in DNA synthesis and induces apoptosis of the cancer cell. Nitiss, J.L. "Targeting DNA topoisomerase II in cancer themotherapy." Nat. Rev. Cancer 9: 338-350 (2009).
In in vitro studies with the H3347 human colon carcinoma cell line, etoposide 4'-phosphate was less toxic than etoposide by a factor of greater than 100. A stronger antitumor response was observed in H3347-bearing mice that were treated with a monoclonal antibody plus L6 (anticarcinoma)-alkaline phosphatase conjugate followed 18-24 hr later by etoposide 4'-phosphate when compared to treatment with etoposide 4'-phosphate or etoposide alone. Senter, P.D., et al. "Anti-tumor effects of antibody-alkaline phosphatase conjugates in combination with etoposide phosphate." Proc. Natl. Acad. Sci. USA 85: 4842-4846 (1988).
Disruption of the murine multidrug resistance protein gene resulted in a two-fold increase in sensitivity to etoposide 4'-phosphate. Lorico, A., et al. "Disruption of the murine MRP (multidrug resistance protein) gene leads to increased sensitivity to etoposide (VP-16) and increased levels of glutathione." Cancer Res. 57: 5238-5242 (1997).
A phase III clinical trial showed that patients with advanced small-cell lung cancer (SCLC) gained a survival benefit and improved quality of life after treatment with the combination of etoposide, carboplatin and paclitaxel. Reck, M., et al. "Efficient palliation in patients with small-cell lung cancer by a combination of paclitaxel, etoposide and carboplatin: quality of life and 6-years'-follow-up results from a randomised phase III trial." Lung Cancer 53: 67-75 (2006).
NOTE: Etoposide 4'-Phosphate, Free Acid is not a phosphate salt of etoposide. The phosphate group is covalently bound to the etoposide moiety, and thus etoposide phosphate is chemically different from etoposide, not merely a different salt form. Etoposide itself is not basic and cannot form an acid addition salt with phosphoric acid or other acids.
Etoposide 4'-phosphate is sometimes referred to, erroneously, as "etoposide 4'-phosphonate." The latter nomenclature is chemically not correct.
Etoposide or its 4'-phosphate derivative are the active ingredients in the drug products sold under the trade name Etopofos® and the other trade names listed above under "Related Terms". These drugs are currently used in patients with a variety of types of cancer, such as non-lymphocytic leukemia, Ewing's sarcoma, testicular cancer, lung cancer, and glioblastoma multiforme. NOTE: THE ETOPOSIDE AND ETOPOSIDE 4'-PHOSPHATE, FREE ACID RESEARCH COMPOUNDS SOLD BY LC LABORATORIES ARE NOT TOPOSAR® NOR ANY OTHER DRUG PRODUCT SPECIFIED BY THE TRADE NAMES LISTED ABOVE UNDER "RELATED TERMS", AND ARE NOT FOR HUMAN USE.
NOTE: the trade names listed above under "Related Terms" are for etoposide- or etoposide 4'-phosphate-containing drug products and they may apply variously to formulations of etoposide or etoposide 4'-phosphate.
Our Etoposide 4'-Phosphate, Free Acid research compound is the free acid, whose CAS number is given above. The CAS number of etoposide itself is 33419-42-0.
Related CAS numbers: the CAS number for the disodium salt of etoposide 4'-phosphate is 122405-33-8. Etoposide 4'-phosphate free acid is more stable than its disodium salt, and the latter is not used clinically.
Other CAS numbers previously assigned to Etoposide 4'-Phosphate, Free Acid, namely 122332-48-3, 138067-47-7, and 149027-99-6, have been deleted by CAS and are no longer in use.
Sold for laboratory or manufacturing purposes only; not for human, veterinary, food, or household use.
Storage: Store at or below -20 ºC. Solubility: Soluble in water and DMSO. Disposal: A
