In Vitro

Kinase Assay:

Cell Assay: 2 × 105 PEL cells are treated with the therapeutic compounds at the indicated doses or with appropriate vehicle as a negative control. Cells are followed for 96 hours, and cell viability is determined by trypan blue exclusion performed in quadruplicate.

Miltefosine is an alkylphosphocholine drug with demonstrated activity against various parasite species and cancer cells as well as some pathogenic bacteria and fungi. Miltefosine inhibits PKC from NIH3T3 cells in cell-free extracts with a IC50 of about 7 μM. Miltefosine targets HIV infected macrophages, which play a role in vivo as long-lived HIV-1 reservoirs. Miltefosine acts by inhibiting the PI3K/Akt pathway, thus removing the infected macrophages from circulation, without affecting healthy cells. Miltefosine inhibits the PI3K/Akt survival pathway in carcinoma cell lines. Miltefosine causes skeletal muscle insulin resistance in vitro by interfering with the insulinsignalling pathway and inhibiting insulin-stimulated glucose uptake. Miltefosine inhibits insulin-stimulated Akt phosphorylation in a dose-dependent manner with 75% inhibition at 40 μM and 98% inhibition at 60 μM.

In Vivo

Miltefosine inhibits anti-IgE induced histamine release from human skin mast cells. Miltefosine can reduce cytokines IL-1β, IL-4, and IL-6 in certain skin tissue cells and also strongly impede the esterification of cholesterol

Animal model

BC-1 cells xenografted NOD-SCID mice

Formulation & Dosage

Formulated inPBS; 50 mg/kg; i.p.

References

[1] Meuillet EJ, et al. Mol Cancer Ther, 2010, 9(3), 706-717.