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Miltefosine

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Chemical Structure| 58066-85-6 同义名 : HePC;Hexadecyl phosphocholine;Miltefosinum;Miltefosina;Miltefosin;Choline Phosphate Hexadecyl Ester Hydroxide Inner Salt;Miltex;mpavido;Miltefosin CHePCHexadecylphosphocholineHDPCHexadecylphosphorylcholineMiltefosinum;NSC 605583;HPC
CAS号 : 58066-85-6
货号 : A288826
分子式 : C21H46NO4P
纯度 : 98%
分子量 : 407.568
MDL号 : MFCD00133396
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 3 mg/mL(7.36 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 30 mg/mL(73.61 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：
生物活性
靶点

  • Akt
描述 Akt/PKB is a crucial protein within the phosphatidylinositol3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) intracellular signalling pathway, which is involved in cell survival. Miltefosine is considered an inhibitor of Akt and is the only oral drug to treat infections caused by L. donovani[7]. Miltefosine belongs to the class of alkylphosphocholine drugs (ALPs), which are phosphocholine esters of aliphatic long-chain alcohols. These alkylphosphocholine compounds are structurally related to the group of alkyl-lysophospholipids, which are synthetic analogues of lysophosphatidylcholines or lysolecithins. From a functional point of view, miltefosine is considered an inhibitor of Akt. The most prominent molecular targets for miltefosine’s anticancer activity are related to the antileishmanial targets, and include the inhibition of phosphatidylcholine biosynthesis and the induction of apoptosis by inhibition of the PI3K/Akt/PKB pathway[8]. The ED50 values of Miltefosine towards inhibiting PI3K/Akt activity are 17.2 μM and 8.1 μM in carcinoma cell lines A431 and HeLa[9]. Miltefosine is approvaled for application in cutaneous metastasis of breast cancer and visceral and cutaneous leishmaniasis. ALPs have also shown in vitro and in vivo activity against Trypanosoma spp., amoebae, Tricomonas vaginalis, Schistosoma mansoni, HIV, and some fungi and bacteria species[10].
作用机制 The mechanism of action of ALPs is not fully understood, they interfere with lipid homeostasis which increased degradation of lipid-droplets via lipophagy and prevent plasma membrane recruitment of the PH domain of AKT by disrupting plasma membrane microdomains thus leading to cell apoptosis[10].
实验方案
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
参考文献

[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.