Repositioning Candidate Details
| Candidate ID: | R1197 |
| Source ID: | DB09031 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Miltefosine |
| Synonyms: | HDPC; hexadecyl 2-(trimethylazaniumyl)ethyl phosphate; Hexadecylphosphocholine; Hexadecylphosphorylcholine; Miltefosine; Monohexadecylphosphocholine; Monohexadecylphosphorylcholine |
| Molecular Formula: | C21H46NO4P |
| SMILES: | CCCCCCCCCCCCCCCCOP([O-])(=O)OCC[N+](C)(C)C |
| Structure: |
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| DrugBank Description: | Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid drug that was originally developed in the 1980s as an anti-cancer agent. It is currently the only recognized oral agent used to treat visceral, cutaneous, and mucosal forms of leishmaniasis, a neglected tropical disease. It can be administered topically or orally and is only indicated in patients aged 12 years or older. The CDC has also recommended it as a first line treatment for free-living amebae (FLA) infections such as primary amebic meningoencephalitis and granulomatous amebic encephalitis. |
| CAS Number: | 58066-85-6 |
| Molecular Weight: | 407.576 |
| DrugBank Indication: | For the treatment of mucosal (caused by Leishmania braziliensis), cutaneous (caused by L. braziliensis, L. guyanensis, and L. panamensis), and visceral leishmaniasis (caused by L. donovani). In comparing Leishmania drug susceptibility, it has been found that L. donovani is the most susceptible to miltefosine while L. major is the least susceptible. Off-label use includes treatment of free-living amebae (FLA) infections (unlabeled use; CDC, 2013). |
| DrugBank Pharmacology: | Little is known about the clinical pharmacodynamics of miltefosine and other antileishmanial drugs. |
| DrugBank MoA: | Miltefosine has demonstrated activity against Leishmania parasites and neoplastic cells primarily due to its effects on apoptosis and disturbance of lipid-dependent cell signalling pathways. Several potential antileishmanial mechanisms of action have been proposed, however no mechanism has been identified definitely. Within the mitochondria, miltefosine inhibits cytochrome-c oxidase leading to mitochondrial dysfunction and apoptosis-like cell death. Antineoplastic mechanisms of action are related to antileishmanial targets and include inhibition of phosphatidylcholine biosynthesis and inhibition of Akt (also known as protein kinase B), which is a crucial protein within the PI3K/Akt/mTOR intracellular signalling pathway involved in regulating the cell cycle. Animal studies also suggest it may be effective against Trypanosome cruzi (the organism responsible for Chagas' disease), metronidazole-resistant strains of Trichonomas vaginalis, and it may have broad-spectrum anti-fungal activity. |
| Targets: | P-glycoprotein 1 |
| Inclusion Criteria: | Therapeutic strategy associated |
