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| Names | |
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| IUPAC name β-D-Glucopyranosyl N,N′-bis(2-chloroethyl)phosphorodiamidate | |
| Systematic IUPAC name (2S,3R,4S,5S,6R)-3,4,5-Trihydroxy-6-(hydroxymethyl)oxan-2-yl N,N′-bis(2-chloroethyl)phosphorodiamidate | |
| Other names β-D-glucosylisophosphoramide mustard | |
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| Properties | |
| Chemical formula | C10H21Cl2N2O7P |
| Molar mass | 383.16 g·mol |
| Except where otherwise noted, data are given for materials in their standard state (at 25 °C , 100 kPa). Infobox references | |
Glufosfamide, also known as glucophosphamide, D-glucose isophosphoramide mustard, D-19575 is an experimental cytotoxic chemotherapeutic agent for treatment of malignancies.
Chemical structure
Glufosfamide is, basically, a glycosidic conjugate between β-D-glucose and the active alkylating moiety of the well-known antineoplastic drug ifosfamide, so-called "isophosphoramide mustard".
Theoretical advantages
Glufosfamide, being a conjugate of glucose and active alkylating moiety of ifosfamide, has the better cell permeability than the parent compound — ifosfamide — or its metabolites. Glufosfamide utilizes the normal cell glucose transport mechanism (a sodium-dependent glucose/sodium co-transporter) for its own transport into the cell. And the glucose uptake mechanism is grossly overexpressed and upregulated in certain cancer cell lines, especially pancreatic cancer, non-small cell lung cancer, and glioblastoma multiforme. This, theoretically, should render them more sensitive to the alkylating effects of glufosfamide while relatively sparing (doing relatively little collateral damage) to the normal cells in which the glucose uptake mechanism is not so upregulated.
Clinical trials
Glufosfamide demonstrated modest efficacy in Phase I and Phase II clinical trials in the treatment of pancreatic cancer, non-small cell lung cancer and recurrent glioblastoma multiforme. A large Phase III trial comparing glufosfamide against 5-FU, both in combination with gemcitabine, for second line treatment of metastatic pancreatic cancer (NCT01954992) is currently active.
References
- Mazur, Lidia; Opydo-Chanek, Małgorzata; Stojak, Marta (2011). "Glufosfamide as a new oxazaphosphorine anticancer agent". Anti-Cancer Drugs. 22 (6): 488–493. doi:10.1097/CAD.0b013e328345e1e0. PMID 21427562. S2CID 398165.
- "Glufosfamide: Beta-D-GLC-IPM, D 19575". Drugs in R&D. 6 (1): 49–52. 2005. doi:10.2165/00126839-200506010-00006. PMID 15801867.
- Liang, J.; Huang, M.; Duan, W.; Yu, X. Q.; Zhou, S. (2007). "Design of new oxazaphosphorine anticancer drugs". Current Pharmaceutical Design. 13 (9): 963–978. doi:10.2174/138161207780414296. PMID 17430192.