Miltefosine  (Synonyms: HePC; Hexadecyl phosphocholine)

Miltefosine is a broad spectrum antimicrobial, anti-leishmanial, phospholipid agent acting by inhibiting the PI3K/Akt activity^[1][2][3][4]. Miltefosine is an inhibitor of CTP-phosphocholine cytidyltransferase (CCT)^[5].

Treatment of HIV-1 infected macrophages with Miltefosine inhibits the recruitment of PH-AktGFP to the plasma membrane. Since Miltefosine inhibits Akt through mimicry of the PH domain, it is likely that Miltefosine binds to PIP3, blocking the recruitment of PH-Akt to the membrane^[1]. Miltefosine (HePC) inhibits protein kinase C (PKC) from NIH3T3 cells in cell-free extracts with a IC₅₀ of about 7 μM. Inhibition is competitive with regard to phosphatidylserine with a K_i of 0.59 μM^[2]. Miltefosine is an alkylphospholipid that inhibit activation of Akt. Miltefosine is a direct inhibitor of Akt, and induces dose-dependent inhibition of primary effusion lymphoma (PEL) in culture and also inhibits the downstream targets of Akt, such as mTOR, leading to reduced phosphorylation and activation of S6K and S6. Importantly, Miltefosine also inhibits Akt targets that are not part of the mTOR pathway, eg, FOXO1, and are therefore expected to have a greater therapeutic impact than mTORC1 inhibitors alone^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mice are randomized into groups of 5 and injected intraperitoneally 5 days a week with 50 mg/kg of either Miltefosine or Perifosine dissolved in PBS, or equivalent volume of vehicle (PBS). Both Miltefosine and Perifosine inhibit the growth rate of tumors compared with vehicle-treated mice. By day 14 after treatment, there is an approximately 50% decrease in average tumor volume in Perifosine- and Miltefosine-treated mice, compared with vehicle-treated mice (P<0.04). Tumor growth is also significantly retarded (P<0.04 for Perifosine and P≤0.055 for Miltefosine by linear mixed-effects model analysis). Immunohistochemical analyses display an overall reduction in staining for phosphorylated ribosomal S6 protein in tumor sections from Miltefosine- and Perifosine-treated mice compared with the PBS-treated mice. This reduced phosphorylation correlated with the delay in tumor progression in drug-treated animals^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

407.57

C₂₁H₄₆NO₄P

58066-85-6

Solid

White to off-white

O=P(OCC[N+](C)(C)C)(OCCCCCCCCCCCCCCCC)[O-]

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Chugh P, et al. Akt inhibitors as an HIV-1 infected macrophage-specific anti-viral therapy. Retrovirology. 2008 Jan 31;5:11  [Content Brief]

  [2]. Uberall F, et al. Hexadecylphosphocholine inhibits inositol phosphate formation and protein kinase C activity. Cancer Res. 1991 Feb 1;51(3):807-12.  [Content Brief]

  [3]. Bhatt AP, et al. Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas. Blood. 2010 Jun 3;115(22):4455-63.  [Content Brief]

  [4]. Eissa MM, et al. Miltefosine Lipid Nanocapsules for Single Dose Oral Treatment of Schistosomiasis Mansoni: A Preclinical Study. PLoS One. 2015 Nov 17;10(11):e0141788  [Content Brief]

  [5]. de Freitas-Junior PR, et al. Effects of miltefosine on the proliferation, ultrastructure, and phospholipid composition of Angomonas deanei, a trypanosomatid protozoan that harbors a symbiotic bacterium. FEMS Microbiol Lett. 2012 Aug;333(2):129-37.  [Content Brief]