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Chemical Structure| 58066-85-6 Chemical Structure| 58066-85-6

Structure of Miltefosine
CAS No.: 58066-85-6

Chemical Structure| 58066-85-6

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Miltefosine is a mult-target inhibitor which can inhibit Akt, PI3K and PKC.

Synonyms: HePC; Hexadecyl phosphocholine; Miltefosinum

4.5 *For Research Use Only !

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Product Citations

Product Citations

Carla B. Hartman ; Phelelisiwe S. Dube ; Lesetja J. Legoabe ; Natascha Van Pelt ; An Matheeussen ; Guy Caljon , et al.

Abstract: Several quinoline derivatives incorporating arylnitro and aminochalcone moieties were synthesized and evaluated in vitro against a broad panel of trypanosomatid protozoan parasites responsible for sleeping sickness (Trypanosoma brucei rhodesiense), nagana (Trypanosoma brucei brucei), Chagas disease (Trypanosoma cruzi), and leishmaniasis (Leishmania infantum). Several of the compounds demonstrated significant antiprotozoal activity. Specifically, compounds 2c, 2d, and 4i displayed submicromolar activity against T. b. rhodesiense with half-maximal effective concentration (EC50) values of 0.68, 0.8, and 0.19 µM, respectively, and with a high selectivity relative to human lung fibroblasts and mouse primary macrophages (∼100-fold). Compounds 2d and 4i also showed considerable activity against T. b. brucei with EC50 values of 1.4 and 0.4 µM, respectively.

Keywords: anti‐infectives ; arylnitro ; chalcones ; protozoal ; quinoline

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Product Details of Miltefosine

CAS No. :58066-85-6
Formula : C21H46NO4P
M.W : 407.57
SMILES Code : O=P(OCC[N+](C)(C)C)(OCCCCCCCCCCCCCCCC)[O-]
Synonyms :
HePC; Hexadecyl phosphocholine; Miltefosinum
MDL No. :MFCD00133396
InChI Key :PQLXHQMOHUQAKB-UHFFFAOYSA-N
Pubchem ID :3599

Safety of Miltefosine

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H334
Precautionary Statements:P261-P264-P270-P285-P301+P310-P304+P341-P330-P342+P311-P405-P501
Class:6.1
UN#:2811
Packing Group:

Related Pathways of Miltefosine

epigenetics
PI3K-AKT

Isoform Comparison

Biological Activity

Target
  • Akt

In Vitro:

Cell Line
Concentration Treated Time Description References
RAW264.7 macrophage cell line 5 μM 24 h Assessment of NO accumulation in macrophages post-infection PMC9713291
Human eosinophils 20 μM 15 min Inhibited CCL11-stimulated Akt phosphorylation PMC9328393
Human eosinophils 20 μM 15 min Inhibited CCL24-induced eosinophil chemotaxis PMC9328393
Human eosinophils 20 μM 15 min Inhibited CCL24-induced CD11b up-regulation by approximately 50% PMC9328393
Mouse bone marrow-derived eosinophils 20 μM 1 min Inhibited CCL24-stimulated intracellular calcium flux by approximately 50%, similar to human eosinophils PMC9328393
Human eosinophils 20 μM 1 min Inhibited CCL24-stimulated intracellular calcium flux by approximately 50% PMC9328393
Human eosinophils 20 μM 15 min Suppressed C5a-induced CD63 expression (0.5 nM) but had no effect at high C5a concentration (100 nM) PMC9328393
Human eosinophils 0.5–20 μM 15 min Inhibited CCL11-induced eosinophil shape change by approximately 50% at the highest concentration (20 μM) PMC9328393
Horse erythrocytes 12 μM 20 hours To assess the effect of miltefosine on the hemolytic activity of A. baumannii strains. Results showed that miltefosine significantly reduced the hemolytic activity of all tested strains. PMC6325191
A549 human alveolar epithelial cells 12 μM 20 hours To assess the effect of miltefosine on the cytolytic activity of A. baumannii strains against A549 cells. Results showed that miltefosine significantly reduced the cytolytic activity of all tested strains. PMC6325191
Trypanosoma cruzi trypomastigotes 31.17 µM 24 hours Evaluate the trypanocidal activity of MLT on trypomastigotes, results showed low trypanocidal activity of MLT. PMC9294734
Trypanosoma cruzi trypomastigotes 31.17 µM (IC50) 24 hours Evaluate the trypanocidal activity of MLT on trypomastigotes, results showed low trypanocidal activity of MLT. PMC9294734
Clonorchis sinensis newly excysted juvenile worms (CsNEJs) 12.5, 25, 50, 100 µM 24, 48, 72 hours To assess the larvicidal effect of MLT on CsNEJs. Results showed that MLT significantly reduced the viability of CsNEJs at 50 µM and 100 µM concentrations, with 0% survival after 48 hours. PMC11373209
Clonorchis sinensis metacercariae (CsMC) 12.5, 25, 50, 100 µM 24, 48, 72 hours To assess the larvicidal effect of MLT on CsMC. Results showed that MLT significantly reduced the viability of CsMC at 50 µM and 100 µM concentrations, with 31.3% and 75% reductions in viability after 72 hours, respectively. PMC11373209
Leishmania infantum promastigotes 10 μM 3.5 h or 5.0 h Measurement of intracellular miltefosine accumulation levels PMC9713291
CAR-T cells 15 μM 4 days Restores CAR-T cell function, enhances glycolytic metabolism and glucose uptake PMC11722131
CCD-18Co 10 μM 48 hours To evaluate the cytotoxic effect of Miltefosine on normal colon cells, results showed that Miltefosine had no significant toxicity on normal cells at higher concentrations. PMC8567043
SW480 1 μM 48 hours To evaluate the cytotoxic effect of Miltefosine on CRC cells, results showed that Miltefosine significantly inhibited the growth of SW480 cells and induced apoptosis. PMC8567043
DLD1 1 μM 48 hours To evaluate the cytotoxic effect of Miltefosine on CRC cells, results showed that Miltefosine significantly inhibited the growth of DLD1 cells and induced apoptosis. PMC8567043
HCT116 1 μM 48 hours To evaluate the cytotoxic effect of Miltefosine on CRC cells, results showed that Miltefosine significantly inhibited the growth of HCT116 cells and induced apoptosis. PMC8567043
HT29 1 μM 48 hours To evaluate the cytotoxic effect of Miltefosine on CRC cells, results showed that Miltefosine significantly inhibited the growth of HT29 cells and induced apoptosis. PMC8567043
Vero-C76 cells 0.51 µM 5 days Evaluate the inhibitory activity of MLT on intracellular amastigotes, results showed significant inhibition of amastigotes by MLT. PMC9294734
Vero-C76 cells 0.51 µM (IC50) 5 days Evaluate the inhibitory activity of MLT on intracellular amastigotes, results showed significant inhibition of amastigotes by MLT. PMC9294734
L. donovani intramacrophagic amastigotes 5.60 µM (EC50) 72 hours Evaluate the leishmanicidal effects of NFT and MTF alone and in combination on L. donovani intramacrophagic amastigotes, finding a strong synergistic effect for the NFT/MTF 1/30 combination up to 50% fa. PMC9865052
L. donovani axenic amastigotes 0.63 µM (EC50) 72 hours Evaluate the leishmanicidal effects of NFT and MTF alone and in combination on L. donovani axenic amastigotes, finding a synergistic effect for the NFT/MTF 1/30 combination. PMC9865052
Lomentospora prolificans FMR 3569 4 µg/ml 72 hours Evaluate the inhibitory effect of Miltefosine on Lomentospora prolificans, results showed effective inhibition of fungal growth PMC8343104
Scedosporium dehoogii CBS 117406 4 µg/ml 72 hours Evaluate the inhibitory effect of Miltefosine on Scedosporium dehoogii, results showed effective inhibition of fungal growth PMC8343104
Scedosporium apiospermum CBS 117407 4 µg/ml 72 hours Evaluate the inhibitory effect of Miltefosine on Scedosporium apiospermum, results showed effective inhibition of fungal growth PMC8343104
Scedosporium boydii CBS 120157 2 µg/ml 72 hours Evaluate the inhibitory effect of Miltefosine on Scedosporium boydii, results showed effective inhibition of fungal growth PMC8343104
Scedosporium aurantiacum CBS 136046 2–4 µg/ml 72 hours Evaluate the inhibitory effect of Miltefosine on Scedosporium aurantiacum, results showed effective inhibition of fungal growth PMC8343104
Cryptococcus gattii ATCC 56990 1 μg/ml 72 hours To evaluate the effects of miltefosine on Cryptococcus cell ultrastructure, results showed thinner cell walls, reduced capsule, and mitochondrial swelling. PMC6105859
Cryptococcus neoformans H99 1 μg/ml 72 hours To evaluate the effects of miltefosine on Cryptococcus cell ultrastructure, results showed thinner cell walls, reduced capsule, and mitochondrial swelling. PMC6105859
Leishmania donovani miltefosine-resistant clone (HePC-R40) promastigotes 69.1 ± 1.1 μM (IC50) 72 hours To assess the effect of miltefosine on the viability of Leishmania donovani resistant clone promastigotes, showing that miltefosine had no cytotoxic effect at concentrations up to 40 μM, but exhibited cytotoxicity at higher doses. PMC353131
Leishmania donovani wild-type promastigotes 13.6 ± 2.0 μM (IC50) 72 hours To assess the effect of miltefosine on the viability of Leishmania donovani promastigotes, showing that miltefosine inhibits the viability of wild-type promastigotes in a concentration-dependent manner. PMC353131

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
NPG mice NCI-H226-luciferase CDX model Intraperitoneal injection 10 mg/kg Once daily, duration as observed Enhances the solid tumor clearance ability of CAR-T cells PMC11722131
NSG mice CRC xenograft model Intraperitoneal 10 mg/kg Daily for 21 days To evaluate the antitumor effect of Miltefosine on CRC xenograft models, results showed that Miltefosine significantly inhibited tumor growth and reduced tumor regrowth potential. PMC8567043
Galleria mellonella G. mellonella infection model Injection 12 μM Single injection, observed for 5 days To assess the effect of miltefosine on the survival rate of G. mellonella infected with A. baumannii. Results showed that miltefosine significantly reduced the mortality rate of infected larvae. PMC6325191
BALB/c mice Eosinophil migration model in IL-5 transgenic mice Oral 20 mg/kg For three consecutive days Significantly suppressed CCL24-induced eosinophil migration into bronchoalveolar lavage fluid PMC9328393
Syrian golden hamsters Clonorchis sinensis infection model Oral 20 mg/kg Administered at 1 and 4 weeks post-infection To evaluate the larvicidal and adulticidal effects of MLT in vivo against Clonorchis sinensis. Results showed that MLT significantly reduced worm burden by 36.7% and 46.9% when administered at 1 and 4 weeks post-infection, respectively. PMC11373209
Swiss mice Immunosuppressed murine model of systemic/vascular pythiosis Oral 25 mg/kg Every 24 hours for 14 days To evaluate the efficacy of miltefosine in treating systemic pythiosis in immunosuppressed mice, results showed miltefosine did not significantly reduce mortality. PMC6325207
BALB/cJ mice Acute infection model Oral 25, 50, 75, 100 mg/kg/day Once daily for 20 consecutive days Evaluate the efficacy of MLT alone or in combination with BZ in acute infection in mice, results showed MLT significantly reduced parasitemia and mortality. PMC9294734
Balb/c mice L. donovani visceral leishmaniasis model Oral NFT: 50 mg/kg bw bid, MTF: 10 mg/kg bw qd 10 days Evaluate the therapeutic efficacy of the NFT/MTF combination in L. donovani-infected mice, showing significant reduction in parasite load, particularly in thymus and bone marrow. PMC9865052

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT06514560 Cutaneous Leishmaniases RECRUITING 2026-12-30 Africa Leprosy, Tuberculosis, ... More >>Rehabilitation and Training (ALERT) Hospital, Addis Abeba, Ethiopia Less <<
NCT02431429 Mucocutaneous Leishmaniasis COMPLETED 2019-03-01 Funderama, Santa Cruz, Bolivia
NCT02429505 Leishmaniasis WITHDRAWN 2025-03-20 Fast-Track Drugs and Biologics... More >>, LLC, Poolesville, Maryland, 20837, United States Less <<
NCT02431143 Visceral Leishmaniasis PHASE2 COMPLETED 2025-09-16 Kacheliba Hospital, Kacheliba,... More >> Rift Valley, West Pokot, 30601, Kenya|Amudat Hospital, Amudat, Karamoja, Uganda Less <<
NCT02193022 Post Kala Azar Dermal Leishman... More >>iasis Less << PHASE3 COMPLETED 2019-06-30 International Centre for Diarr... More >>heal Disease Research, Bangladesh, Dhaka, 1212, Bangladesh Less <<
NCT02429518 Mucocutaneous Leishmaniasis COMPLETED 2018-03-06 Funderma, Santa Cruz, Bolivia
NCT01050907 Mucosal Leishmaniasis|Cutaneou... More >>s Leishmaniasis Less << PHASE2 COMPLETED 2025-03-15 For this treatment IND, each P... More >>hysician entered patients at his/her own facility. Below data is for protocol central contact:, Bethesda, Maryland, 20852, United States|NIH, Bethesda, Maryland, 20892, United States Less <<
NCT02687971 Cutaneous Leishmaniasis PHASE2 COMPLETED 2019-09-10 Programa de Estudios y Control... More >> de Enfermedades Tropicales (PECET), Universidad de Antioquia, Medellin, Colombia|IMT Alexander Von Humboldt, Lima, Peru Less <<
NCT02427308 Leishmaniasis or Other Uses of... More >> Miltefosine Less << RECRUITING 2025-03-26 Fast Track, North Potomac, Mar... More >>yland, United States Less <<
NCT01462500 Cutaneous Leishmaniasis PHASE4 COMPLETED 2025-12-15 Corporación Centro Internacion... More >>al de entrenamiento e Investigaciónes Médicas, Cali, Valle, 5930, Colombia Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.45mL

0.49mL

0.25mL

12.27mL

2.45mL

1.23mL

24.54mL

4.91mL

2.45mL

References

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

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

[3]Botschuijver S, van Diest SA, et al. Miltefosine treatment reduces visceral hypersensitivity in a rat model for irritable bowel syndrome via multiple mechanisms. Sci Rep. 2019 Aug 29;9(1):12530.

[4]Bhatt AP, Bhende PM, 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.

[5]Manna L, Corso R, et al. Long-term follow-up of dogs with leishmaniosis treated with meglumine antimoniate plus allopurinol versus miltefosine plus allopurinol. Parasit Vectors. 2015 May 28;8:289.

[6]Miltefosine

[7]Pinto-Martinez AK, Rodriguez-Durán J, Serrano-Martin X, Hernandez-Rodriguez V, Benaim G. Mechanism of Action of Miltefosine on Leishmania donovani Involves the Impairment of Acidocalcisome Function and the Activation of the Sphingosine-Dependent Plasma Membrane Ca2+ Channel. Antimicrob Agents Chemother. 2017 Dec 21;62(1):e01614-17.

[8]Dorlo TP, Balasegaram M, Beijnen JH, de Vries PJ. Miltefosine: a review of its pharmacology and therapeutic efficacy in the treatment of leishmaniasis. J Antimicrob Chemother. 2012 Nov;67(11):2576-97.

[9]Uberall F, Oberhuber H, Maly K, Zaknun J, Demuth L, Grunicke HH. Hexadecylphosphocholine inhibits inositol phosphate formation and protein kinase C activity. Cancer Res. 1991 Feb 1;51(3):807-12.

[10]Pachioni Jde A, Magalhães JG, Lima EJ, Bueno Lde M, Barbosa JF, de Sá MM, Rangel-Yagui CO. Alkylphospholipids - a promising class of chemotherapeutic agents with a broad pharmacological spectrum. J Pharm Pharm Sci. 2013;16(5):742-59.

 

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