529:(NSCLC). 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'. A phase II trial for the treatment of brain cancers was also reported. 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.
239:
24:
558:. 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.
366:
537:
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
1249:
1253:
1108:
Shafer, SH; Williams CL (2003). "Non-small and small cell lung carcinoma cell lines exhibit cell type-specific sensitivity to edelfosine-induced cell death and different cell line-specific responses to edelfosine treatment".
576:"The antitumor ether lipid Edelfosine (ET-18-O-CH3) induces apoptosis in H-ras transformed human breast epithelial cells: by blocking ERK1/2 and p38 mitogenactivated protein kinases as potential targets"
1289:
Drings, P; Günther I; Gatzmeier U; ulbrich F; et al. (1992). "Final
Evaluation of a Phase II Study on the Effect of Edelfosine (an Ether Lipid) in Advanced Non-Small-Cell Bronchogenic Carcinoma".
668:
Gajate, C; Mollinedo F (2002). "Biological
Activities, Mechanisms of Action and Biomedical Prospect of the Antitumor Ether Phospholipid ET-18-OCH3 (Edelfosine), A Proapoptotic Agent in Tumor Cells".
722:
Mollinedo, F; Gajate C; Martín-Santamaria S; Gago F (2004). "ET-18-OCH3 (edelfosine): a selective antitumour lipid targeting apoptosis through intracellular activation of Fas/CD95 death receptor".
1223:
800:
Munder, PG; Modolell M; Andreesen R; Weltzien HU; Westphal O (1979). "Lysophosphatidylcholine ( Lysolecithin ) and its
Synthetic Analogues. Immunemodulating and Other Biologic Effects".
970:
Noseda, A; Berens ME; White JG; Modest EJ (1988). "In vitro antiproliferative activity of combinations of ether lipid analogues and DNA-interactive agents against human tumor cells".
757:
Ruiter, GA; Zerp SF; Bartelink H; Blitterswijk WJ van; Verheij M (2003). "Anti-cancer alkyl-lysophospholipids inhibit the phosphatidylinositol 3-kinase-Akt/PKB survival pathway".
379:
513:
biodistribution studies demonstrated a “considerably higher” accumulation of
Edelfosine in tumor cells than in other analyzed organs. It remained undergraded for a long time.
448:(PKB) survival pathway. Aside from these plasma-level effects, edelfosine also affects gene expression by modulating the expression and activity of transcription factors.
620:
Vogler, William R.; Liu, Jianguo; Volpert, Olga; Ades, Edwin W.; Bouck, Noel (1998). "The anticancer drug edelfosine is a potent inhibitor of neovascularization in vivo".
100:
1275:
1416:
Edelfosine and perifosine induce selective apoptosis in multiple myeloma by recruitment of death receptors and downstream signaling molecules into lipid rafts
285:
575:
1440:
1227:
1362:
Munder, PG; Ferber E; Modolell M; Fischer H. (1969). "The influence of various adjuvants on the metabolism of phospholipids in macrophages".
1146:"Antitumor alkyl ether lipid edelfosine: tissue distribution and pharmacokinetic behavior in healthy and tumor-bearing immunosuppressed mice"
1185:
Arnold, B; Reuther R; Weltzien HU (1978). "Distribution and metabolism of synthetic alkyl analogs of lysophosphatidylcholine in mice".
272:
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
262:
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
505:
activity against human solid tumors in mice was shown against malignant gynecological tumor cells, like ovarian cancer, and against
253:
1401:
Edelfosine-induced metabolic changes in cancer cells that precede the overproduction of reactive oxygen species and apoptosis. 2010
837:"Targeting the PI3K/Akt cell survival pathway to induce cell death of HIV-1 infected macrophages with alkylphospholipid compounds"
1224:"A Phase I/II trial of edelfosine purging of autologous bone marrow transplantation (ABMT) in acute leukemia (Meeting abstract)"
1426:
Sensitivity of K562 and HL-60 Cells to
Edelfosine, an Ether Lipid Drug, Correlates with Production of Reactive Oxygen Species
1410:
542:
observed. Those findings in animals were confirmed in clinical trials. No mutagenic or cytogenetic effects were observed.
935:
Klein-Franke, A; Munder PG (1992). "Alkyllysophospholipid prevents induction of experimental allergic encephalomyelitis".
526:
386:
196:
217:
1415:
1032:
Vogler, WR; Berdel WE (1993). "Autologous bone marrow transplantation with alkyl-lysophospholipid-purged marrow".
1411:
Effect of the lysophospholipid analogues edelfosine, ilmofosine and miltefosine against
Leishmania amazonensis.
582:
1421:
Novel Anti-Inflammatory Action of
Edelfosine Lacking Toxicity with Protective Effect in Experimental Colitis
551:
406:
1445:
140:
593:
36:
997:
Berdel, WE (1990). "Ether lipids and derivatives as investigational anticancer drugs. A brief review".
1450:
848:
234:
66:
1406:
Edelfosine, apoptosis, MDR and Na+/H+ exchanger: Induction mechanisms and treatment implications.
1344:
817:
782:
1425:
1379:
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1167:
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1090:
1049:
1014:
979:
952:
917:
876:
774:
739:
695:
637:
497:
Edelfosine apoptosis-inducing abilities were studied with several types of cancer, among them
451:
It has immune modulating properties. These characteristics cause edelfosine also to affect
1371:
1328:
1298:
1194:
1157:
1144:
Estella-Hermoso de
Moendoza, A; Campanero M a; Iglesi-Vincente J de la; et al. (2009).
1118:
1080:
1041:
1006:
944:
907:
866:
856:
809:
766:
731:
685:
677:
629:
498:
445:
308:
205:
76:
606:
521:
Several clinical trials were conducted. Among them a phase I trials with solid tumors or
160:
912:
895:
238:
1420:
852:
120:
1319:
Houlihan, WJ; Lohmeyer M; Workman P; Cheon SH (1995). "Phospholipid antitumor agents".
871:
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357:
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1198:
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506:
417:
821:
786:
1348:
429:
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1145:
861:
185:
555:
475:
468:
1400:
550:
In the 1960s
Herbert Fischer and Paul Gerhard in Freiburg, Germany, found that
467:
Edelfosine and other ALPs can be used for purging residual leukemic cells from
1405:
633:
479:
464:
It can be administered orally, intraperitoneally (IP) and intravenously (IV).
342:
151:
735:
681:
1045:
458:
425:
1332:
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1130:
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641:
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522:
437:
554:(2-lysophosphatidylcholine, LPC) increases the phagocytotic activity of
813:
690:
172:
23:
1375:
1302:
1067:
Mollinedo, PG; Iglesia-Vicente J de la; Gajate C; et al. (2010).
1010:
41:
2-Methoxy-3-(octadecyloxy)propyl 2-(trimethylazaniumyl)ethyl phosphate
131:
356:
Except where otherwise noted, data are given for materials in their
111:
99:
89:
1187:
Biochimica et
Biophysica Acta (BBA) - Lipids and Lipid Metabolism
433:
452:
441:
421:
222:
501:
and non-small and small cell lung carcinoma cell lines.
1364:
International Archives of Allergy and Applied Immunology
374:
428:, sparing healthy cells. Edelfosine can activate the
835:
Lucas, A; Kim Y; Rivera-Pabon O; et al. (2010).
896:"activity of edelfosine, miltefosine and ilmofosine"
457:
It can complement classic anti-cancer drugs such as
900:Basic & Clinical Pharmacology & Toxicology
1069:"Lipid raft-targeted therapy in multiple myeloma"
405:-methyl-glycero-3-phosphocholine) is a synthetic
1314:
1312:
894:Azzouz, S; Maache M; Garcia RG; Osuna A (2005).
717:
715:
713:
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663:
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655:
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184:
75:
1250:"Edelfosin for the treatment of brain tumors"
8:
293:P(=O)(OCC(OC)COCCCCCCCCCCCCCCCCCC)OCC(C)(C)C
235:DTXSID20922896 DTXSID9045766, DTXSID20922896
1274:: CS1 maint: numeric names: authors list (
1218:
1216:
424:. In many tumor cells, it causes selective
237:
159:
15:
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1084:
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870:
860:
689:
204:
416:Like all ALPs, it incorporates into the
567:
455:, parasitic, and autoimmune diseases.
290:
258:
233:
1267:
602:
591:
436:cell death receptor, can inhibit the
265:Key: MHFRGQHAERHWKZ-UHFFFAOYSA-N
139:
119:
7:
913:10.1111/j.1742-7843.2005.pto960109.x
802:Springer Seminars in Immunopathology
175:
335:
14:
1111:International Journal of Oncology
771:10.1097/00001813-200302000-00011
364:
326:
320:
54:-methyl-glycero-3-phosphocholine
22:
360:(at 25 °C , 100 kPa).
1248:United States Patent 6514519.
527:non-small-cell lung carcinomas
329:
314:
1:
1441:Quaternary ammonium compounds
1163:10.1158/1078-0432.CCR-08-1654
949:10.1016/s0896-8411(05)80053-8
1199:10.1016/0005-2760(78)90125-x
862:10.1371/journal.pone.0013121
401:(ET-18-O-CH3; 1-octadecyl-2-
724:Current Medicinal Chemistry
50:ET-18-O-CH3; 1-octadecyl-2-
1467:
1321:Medicinal Research Reviews
440:mitogenic pathway and the
634:10.3109/07357909809032884
354:
301:
281:
249:
59:
47:
35:
30:
21:
1150:Clinical Cancer Research
1034:Journal of Hematotherapy
736:10.2174/0929867043363703
682:10.2174/1389200023337225
420:and does not target the
1046:10.1089/scd.1.1993.2.93
937:Journal of Autoimmunity
670:Current Drug Metabolism
413:(anti-cancer) effects.
1333:10.1002/med.2610150302
1226:. 1996. Archived from
601:Cite journal requires
581:. 2008. Archived from
407:alkyl-lysophospholipid
37:Systematic IUPAC name
1123:10.3892/ijo.23.2.389
1086:10.1038/onc.2010.131
1256:on 14 December 2012
853:2010PLoSO...513121L
474:It is an analog of
350: g·mol
18:
814:10.1007/bf01891668
525:and phase II with
387:Infobox references
16:
1376:10.1159/000230731
1303:10.1159/000217391
1079:(26): 3748–3757.
1011:10.1159/000216771
759:Anti-Cancer Drugs
395:Chemical compound
393:
392:
218:CompTox Dashboard
101:Interactive image
1458:
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446:protein kinase B
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972:Cancer Research
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730:(24): 3163–84.
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649:
619:
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517:Clinical trials
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409:(ALP). It has
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1327:(3): 157–223.
1308:
1297:(5): 375–382.
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1177:
1136:
1117:(2): 389–400.
1100:
1059:
1024:
989:
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808:(2): 187–203.
792:
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676:(3): 491–525.
647:
612:
603:|journal=
588:on 2011-08-11.
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1370:(1): 117–28.
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1230:on 2012-03-08
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1156:(3): 858–64.
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1040:(1): 93–102.
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1005:(4): 245–50.
1004:
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847:(9): e13121.
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628:(8): 549–53.
627:
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622:Cancer Invest
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507:breast cancer
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471:transplants.
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1290:
1284:
1258:. Retrieved
1254:the original
1243:
1232:. Retrieved
1228:the original
1193:(1): 47–55.
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1002:
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943:(1): 83–91.
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594:cite journal
583:the original
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141:ChEMBL107514
60:Identifiers
51:
48:Other names
1451:Zwitterions
906:(1): 60–5.
691:10261/59536
556:macrophages
552:lysolecitin
476:miltefosine
469:bone marrow
302:Properties
121:CHEBI:78649
17:Edelfosine
1435:Categories
1234:2011-02-28
562:References
480:perifosine
399:Edelfosine
343:Molar mass
206:1Y6SNA8L5S
152:ChemSpider
88:3D model (
77:70641-51-9
67:CAS Number
1291:Onkologie
999:Onkologie
523:leukemias
459:cisplatin
426:apoptosis
1270:cite web
1172:19188156
1131:12851688
1095:20418917
1073:Oncogene
922:15667597
881:20927348
841:PLOS ONE
822:42907729
787:42468599
779:12569304
744:15579006
700:12369895
533:Toxicity
487:In vitro
438:MAPK/ERK
1384:4980286
1349:6997551
1341:7658750
1054:7921970
1019:2234777
984:3349458
957:1373062
872:2948033
849:Bibcode
642:9844614
546:History
540:in vivo
511:In vivo
503:In vivo
493:results
491:in vivo
380:what is
378: (
348:523.736
173:PubChem
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286:SMILES
132:ChEMBL
31:Names
1345:S2CID
818:S2CID
783:S2CID
586:(PDF)
579:(PDF)
254:InChI
112:ChEBI
90:JSmol
1380:PMID
1337:PMID
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489:and
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434:CD95
197:UNII
186:1392
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767:doi
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430:Fas
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