Miltefosine

Category	Human immunodeficiency Virus (HIV)
CAS	58066-85-6
Description	Miltefosine inhibits PI3K/Akt activity with ED50 of 17.2 μM and 8.1 μM in carcinoma cell lines A431 and HeLa, first oral drug for Visceral leishmaniasis, effective against both promastigotes and amastigotes.

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Product Information

Synonyms	n-hexadecylphosphocholine; Hexadecylphosphocholine; Miltex; Impavido; 2-[[(Hexadecyloxy)hydroxyphosphinyl]oxy]-N,N,N-trimethylethanaminium; MAPCHO^®-16; C-16Miltefosine
IUPAC Name	hexadecyl 2-(trimethylazaniumyl)ethyl phosphate
Molecular Weight	407.57
Molecular Formula	C21H46NO4P
Canonical SMILES	CCCCCCCCCCCCCCCCOP(=O)([O-])OCC[N+](C)(C)C
InChI	InChI=1S/C21H46NO4P/c1-5-6-7-8-9-10-11-12-13-14-15-16-17-18-20-25-27(23,24)26-21-19-22(2,3)4/h5-21H2,1-4H3
InChIKey	PQLXHQMOHUQAKB-UHFFFAOYSA-N
Melting Point	223-228°C (dec.)
Flash Point	320 °F
Purity	>98%
Solubility	Soluble in Chloroform (Slightly), Methanol (Slightly)
Appearance	White to Off-white Solid
Application	Antineoplastic Agents
Storage	Store at -20°C
Complexity	363
Exact Mass	407.31644595
In Vitro	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. 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 Ki of 0.59 µM. 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.
In Vivo	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.
PSA	68.40000
Target	Akt; HIV
XLogP3-AA	6.7