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CAS No. : 58066-85-6
MCE 国际站:Miltefosine
产品活性:Miltefosine是一种广谱抗微生物,抗利什曼原虫,磷脂剂,通过抑制 PI3K/Akt 活性起作用。Miltefosine 是 CTP 磷酸胆碱胞苷基转移酶 (CCT) 的抑制剂
研究领域:PI3K/Akt/mTOR | Anti-infection
作用靶点:Akt | HIV | Parasite
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.
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货号: HY-13685
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