Names | |
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Preferred 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 | |
3D model (JSmol) | |
ChEBI | |
ChEMBL | |
ChemSpider | |
PubChem CID | |
UNII | |
CompTox Dashboard (EPA) | |
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Properties | |
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). | |
verify (what is ?) | |
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]
Irofulven or 6-hydroxymethylacylfulvene is an experimental antitumor agent. It belongs to the family of drugs called alkylating agents.
Mebendazole (MBZ) is a medication used to treat a number of parasitic worm infestations. This includes ascariasis, pinworm/threadworm disease, hookworm infections, guinea worm infections, hydatid disease, and giardia, among others. It is taken by mouth.
Betulinic acid is a naturally occurring pentacyclic triterpenoid which has antiretroviral, antimalarial, and anti-inflammatory properties, as well as a more recently discovered potential as an anticancer agent, by inhibition of topoisomerase. It is found in the bark of several species of plants, principally the white birch from which it gets its name, but also the ber tree, selfheal, the tropical carnivorous plants Triphyophyllum peltatum and Ancistrocladus heyneanus, Diospyros leucomelas, a member of the persimmon family, Tetracera boiviniana, the jambul, flowering quince, rosemary, and Pulsatilla chinensis.
Miltefosine, sold under the trade name Impavido among others, is a medication mainly used to treat leishmaniasis and free-living amoeba infections such as Naegleria fowleri and Balamuthia mandrillaris. This includes the three forms of leishmaniasis: cutaneous, visceral and mucosal. It may be used with liposomal amphotericin B or paromomycin. It is taken by mouth.
The Fas receptor, also known as Fas, FasR, apoptosis antigen 1, cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the FAS gene. Fas was first identified using a monoclonal antibody generated by immunizing mice with the FS-7 cell line. Thus, the name Fas is derived from FS-7-associated surface antigen.
Sphingosine-1-phosphate (S1P) is a signaling sphingolipid, also known as lysosphingolipid. It is also referred to as a bioactive lipid mediator. Sphingolipids at large form a class of lipids characterized by a particular aliphatic aminoalcohol, which is sphingosine.
Death receptor 5 (DR5), also known as TRAIL receptor 2 (TRAILR2) and tumor necrosis factor receptor superfamily member 10B (TNFRSF10B), is a cell surface receptor of the TNF-receptor superfamily that binds TRAIL and mediates apoptosis.
Carmofur (INN) or HCFU (1-hexylcarbamoyl-5-fluorouracil) is a pyrimidine analogue used as an antineoplastic agent. It is a derivative of fluorouracil, being a lypophilic-masked analog of 5-FU that can be administered orally.
Lysophosphatidylcholines, also called lysolecithins, are a class of chemical compounds which are derived from phosphatidylcholines.
Alky-lysophospholipids (ALP) are synthetic analogues of lysophosphatidylcholines (LPC), also called lysolecithins. They are synthesized by replacing the acyl-group within the LPC with an alkyl-group. They are in contrast to LPC metabolically very stable. They have anti-neoplastic (“anti-cancer”) and immune modulating effects. Their anti-tumor effects are due to modulation of intracellular signalling pathways, inducing apoptosis. It is highly selective, sparing healthy cells. Several like edelfosine, miltefosine and perifosine are under research and development as drugs against cancer and other diseases.
Neutral cholesterol ester hydrolase 1 (NCEH) also known as arylacetamide deacetylase-like 1 (AADACL1) or KIAA1363 is an enzyme that in humans is encoded by the NCEH1 gene.
Elemenes are a group of closely related natural chemical compounds found in a variety of plants. The elemenes, which include α-, β-, γ-, and δ-elemene, are structural isomers of each other and are classified as sesquiterpenes. The elemenes contribute to the floral aromas of some plants, and are used as pheromones by some insects.
Brivanib alaninate (INN/USAN) also known as BMS-582664 is an investigational, anti-tumorigenic drug for oral administration. The drug is being developed by Bristol-Myers Squibb for the treatment of hepatocellular carcinoma or HCC, the most common type of liver cancer.
Linsitinib is an experimental drug candidate for the treatment of various types of cancer. It is an inhibitor of the insulin receptor and of the insulin-like growth factor 1 receptor (IGF-1R). This prevents tumor cell proliferation and induces tumor cell apoptosis.
The tumor microenvironment (TME) is the environment around a tumor, including the surrounding blood vessels, immune cells, fibroblasts, signaling molecules and the extracellular matrix (ECM). The tumor and the surrounding microenvironment are closely related and interact constantly. Tumors can influence the microenvironment by releasing extracellular signals, promoting tumor angiogenesis and inducing peripheral immune tolerance, while the immune cells in the microenvironment can affect the growth and evolution of cancerous cells.
Titanocene Y also known as bis[(p-methoxybenzyl)cyclopentadienyl]titanium(IV) dichloride or dichloridobis(η5- cyclopentadienyl)titanium is an organotitanium compound that has been investigated for use as an anticancer drug.
Cytokine-induced killer cells (CIK) cells are a group of immune effector cells featuring a mixed T- and natural killer (NK) cell-like phenotype. They are generated by ex vivo incubation of human peripheral blood mononuclear cells (PBMC) or cord blood mononuclear cells with interferon-gamma (IFN-γ), anti-CD3 antibody, recombinant human interleukin (IL)-1 and recombinant human interleukin (IL)-2.
Dicycloplatin is a chemotherapy medication used to treat a number of cancers which includes the non-small-cell lung carcinoma and prostate cancer.
Isatuximab, sold under the brand name Sarclisa, is a monoclonal antibody (mAb) medication for the treatment of multiple myeloma.
KP1019, or trans-[tetrachlorobis(1H-indazole)ruthenate(III)], is one of three ruthenium anti-cancer drugs to enter into phase I clinical trials, the others being NAMI-A and TLD-1433. Research into ruthenium-based drugs has provided novel alternatives for platinum-based chemotherapeutics such as Cisplatin and its derivatives. KP1019 is useful for metastatic tumors and cis-platin resistant tumors. It exhibits potent cytotoxicity against primary tumors, particularly in colorectal cancer.
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