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Structure of Miltefosine
CAS No.: 58066-85-6
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The BI-3802 was designed by Boehringer Ingelheim and could be obtained free of charge through the Boehringer Ingelheim open innovation portal opnMe.com, associated with its negative control.
Miltefosine is a mult-target inhibitor which can inhibit Akt, PI3K and PKC.
Synonyms: HePC; Hexadecyl phosphocholine; Miltefosinum
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Novel quinoline derivatives with broad-spectrum antiprotozoal activities
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.
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Keywords: anti‐infectives ; arylnitro ; chalcones ; protozoal ; quinoline
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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 |
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: | Ⅲ |
Target |
|
In Vitro:
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:
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 << |
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 |