Edelfosine

Names
Systematic IUPAC name 2-Methoxy-3-(octadecyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate
Other names ET-18-O-CH3; 1-octadecyl-2-O-methyl-glycero-3-phosphocholine
Identifiers
CAS Number	70641-51-9 N
3D model (JSmol)	Interactive image
ChEBI	CHEBI:78649 N
ChEMBL	ChEMBL107514 N
ChemSpider	1350 Y
PubChem CID	1392
UNII	1Y6SNA8L5S Y
CompTox Dashboard (EPA)	DTXSID20922896 DTXSID9045766, DTXSID20922896
InChI InChI=1S/C27H58NO6P/c1-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-23-32-25-27(31-5)26-34-35(29,30)33-24-22-28(2,3)4/h27H,6-26H2,1-5H3 Y Key: MHFRGQHAERHWKZ-UHFFFAOYSA-N Y InChI=1S/C27H58NO6P/c1-6-7-8-9-10-11-12-13-14-15-16-17-18-19-20-21-23-32-25-27(31-5)26-34-35(29,30)33-24-22-28(2,3)4/h27H,6-26H2,1-5H3
SMILES [O-]P(=O)(OCC(OC)COCCCCCCCCCCCCCCCCCC)OCC[N+](C)(C)C
Properties
Chemical formula	C27H58NO6P
Molar mass	523.736 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

Edelfosine (ET-18-O-CH3; 1-octadecyl-2-O-methyl-glycero-3-phosphocholine)^[1] is a synthetic alkyl-lysophospholipid (ALP). It has antineoplastic (anti-cancer) effects.^[2]

Like all ALPs, it incorporates into the cell membrane and does not target the DNA. In many tumor cells, it causes selective apoptosis, sparing healthy cells.^[3] Edelfosine can activate the Fas/CD95 cell death receptor,^[4] can inhibit the MAPK/ERK mitogenic pathway and the Akt/protein kinase B (PKB) survival pathway.^[3][5] Aside from these plasma-level effects, edelfosine also affects gene expression by modulating the expression and activity of transcription factors.^[3][4]

It has immune modulating properties.^[6] These characteristics cause edelfosine also to affect HIV,^[7] parasitic,^[4][8] and autoimmune diseases.^[4][9]
It can complement classic anti-cancer drugs such as cisplatin.^[10]

It can be administered orally, intraperitoneally (IP) and intravenously (IV).

Edelfosine and other ALPs can be used for purging residual leukemic cells from bone marrow transplants.^[4][11][12]

It is an analog of miltefosine and perifosine.

Edelfosine apoptosis-inducing abilities were studied with several types of cancer, among them multiple myeloma^[13] and non-small and small cell lung carcinoma cell lines.^[14] In vivo activity against human solid tumors in mice was shown against malignant gynecological tumor cells,^[3] like ovarian cancer, and against breast cancer. In vivo biodistribution studies demonstrated a “considerably higher” accumulation of Edelfosine in tumor cells than in other analyzed organs. It remained undergraded for a long time.^[3][15][16]

Several clinical trials were conducted. Among them a phase I trials with solid tumors or leukemias and phase II with non-small-cell lung carcinomas (NSCLC).^[3] In a Phase II clinical trial for use of Edelfosine in treating leukemia with bone marrow transplants, it was found to be safe and 'possibly effective'.^[17] A phase II trial for the treatment of brain cancers was also reported.^[18] It showed encouraging results in stopping the growth of the tumor and a considerable improvement in the “quality of life” of the patients. A phase II trial on the effect of Edelfosine on advanced non-small-cell bronchogenic carcinoma had a “remarkable” “high proportion of patients with stationary tumor status” as result, stable disease after initial progression in 50% of the patients.^[17][19]

In animal tests the main toxic effect was gastrointestinal irritation. There were no significant negative systemic side effects observed. It showed that edelfosine can be given over a long period safely. Most important, in contrast to many DNA-directed anti-cancer drugs, no bone marrow toxicity was in vivo observed. Those findings in animals were confirmed in clinical trials. No mutagenic or cytogenetic effects were observed.^[3][20]

In the 1960s Herbert Fischer and Paul Gerhard in Freiburg, Germany, found that lysolecitin (2-lysophosphatidylcholine, LPC) increases the phagocytotic activity of macrophages. Since LPC had a short half-life, synthetic LPC-analogues were tested by Fischer, Otto Westphal, Hans Ulrich Weltzien and Paul Gerhard Munder. Unexpectedly, some of the substances showed strong anti-tumor activity and among them Edelfosine was the most effective. It is therefore considered to be the prototype of synthetic anti-cancer lipids.^[20][21]

• Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis. 2010
• Edelfosine, apoptosis, MDR and Na+/H+ exchanger: Induction mechanisms and treatment implications.
• Effect of the lysophospholipid analogues edelfosine, ilmofosine and miltefosine against Leishmania amazonensis.
• Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts
• Novel Anti-Inflammatory Action of Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis
• Sensitivity of K562 and HL-60 Cells to Edelfosine, an Ether Lipid Drug, Correlates with Production of Reactive Oxygen Species