Miltefosine-d4 (Synonyms: Hexadecylphosphocholine-d4, HPC-d4)

Miltefosine-d₄ is intended for use as an internal standard for the quantification of miltefosine by GC- or LC-MS. Miltefosine is an inhibitor of CTP:phosphocholine cytidylyltransferase (CCT).¹ It inhibits liposome-induced CCT activity in MDCK cell homogenates when used at concentrations ranging from 10 to 50 µM, as well as induces translocation of CCT from the cell membrane to the cytosol in MDCK cells. Miltefosine inhibits phosphatidylcholine biosynthesis induced by phorbol 12-myristate 13-acetate in MDCK and HeLa cells when used at a concentration of 50 µM.² It inhibits phosphatidylserine-activated PKC (IC₅₀ = 62 µM), as well as PMA-induced morphological changes and proliferation of MDCK cells.³ Miltefosine is active against clinical isolate promastigotes of L. infantum (EC₅₀s = 5-25 µM).⁴ Topical application of miltefosine (0.5%) completely eradicates L. amazonensis and induces re-epithelialization of lesions in a mouse model of cutaneous leishmaniasis.⁵ Formulations containing miltefosine have been used in the treatment of leishmaniasis and various free-living amoeba infections.

1.Geilen, C.C., Wieder, T., and Reutter, W.Hexadecylphosphocholine inhibits translocation of CTP: Choline-phosphate cytidylyltransferase in Madin-Darby canine kidney cellsJ. Biol. Chem.267(10)6719-6724(1992) 2.Wieder, T., Geilen, C.C., and Reutter, W.Antagonism of phorbol-ester-stimulated phosphatidylcholine biosynthesis by the phospholipid analogue hexadecylphosphocholineBiochem. J.291(Pt. 2)561-567(1993) 3.Geilen, C.C., Haase, R., Buchner, K., et al.The phospholipid analogue, hexadecylphosphocholine, inhibits protein kinase C in vitro and antagonises phorbol ester-stimulated cell proliferationEur. J. Cancer27(12)1650-1653(1991) 4.Espada, C.R., de Castro Levatti, E.V., BoitÉ, M.C., et al.In vitro susceptibility to miltefosine of Leishmania infantum (syn. L. chagasi) isolates from different geographical areas in BrazilMicroorganisms9(6)1228(2021) 5.Peralta, M.F., Usseglio, N.A., Bracamonte, M.E., et al.Efficacy of topical Miltefosine formulations in an experimental model of cutaneous leishmaniasisDrug Deliv. Transl. Res.12(1)180-196(2022)