Miltefosine (Impavido; HePC)   中文名称: 米替福星

Akt; PI3K; PKC (IC50 = ~7 μM)

米替福辛是一种烷基磷酸胆碱药物，具有对抗多种寄生虫、癌细胞以及一些病原细菌和真菌的活性。 Miltefosine 可抑制无细胞提取物中 NIH3T3 细胞的 PKC，IC50 约为 7 μM。[1]在体内，感染 HIV 的巨噬细胞是长期存活的 HIV-1 储存库，而米替福辛则针对这些细胞。通过阻断 PI3K/Akt 通路，米替福辛可消除循环中受感染的巨噬细胞，而不损害健康细胞。 [2]在癌细胞系中，米替福辛抑制 PI3K/Akt 存活途径。 [3]米替福辛干扰胰岛素信号通路并阻止胰岛素刺激的葡萄糖摄取，从而导致体外骨骼肌胰岛素抵抗。米替福辛在 40 M 浓度下抑制 75%，在 60 μM 浓度下抑制 98%，以剂量依赖性方式抑制胰岛素刺激的 Akt 磷酸化。 [4]

Miltefosine 抑制抗 IgE 诱导的人皮肤肥大细胞释放组胺。米替福辛可以显着减缓胆固醇的酯化，并降低某些皮肤组织细胞中细胞因子IL-1β、IL-4和IL-6的水平。 [5]

ApoAlert Caspase 荧光检测试剂盒用于测量具有酶活性的 caspase-3 的量。简而言之，将 1106 个 BC-1 PEL 细胞暴露于载体对照、50 M 米替福辛、50 M 哌立福辛或 20 nM NVP-BEZ235。 12小时后，收集细胞并裂解。对于每个样品，将等量的细胞裂解物与荧光 caspase-3 底物 (DEVD-AFC) 一起孵育。将激发和发射滤光片波长分别设置为 400 和 505 nm，Caspase-3 裂解 DEVD 释放 AFC，使用 FLUOstar OPTIMA 荧光计测量其荧光。

× 105 PEL 细胞要么用推荐剂量的治疗物质处理，要么用适当的载体作为阴性对照。台盼蓝排除一式四份进行，以评估 96 小时细胞监测后的细胞活力。

Mice: PEL cells are collected, counted, and diluted in 100 L of PBS combined with 100 L of Matrigel depleted of growth factors after being washed in ice-cold phosphate buffered saline. Subcutaneous injection of 1 105 to 7.5 105 BC-1 cells is made into the right flank of NOD. Alternatively, CB17-Prkdcscid/J mice. On alternate days, the mice are checked for the development of palpable tumors (2 mm3). If this occurs, drug or vehicle treatments are started, and the mice receive either intraperitoneal (Perifosine) or oral gavage (Rosiglitazone, NVP-BEZ235) treatments 5 days a week. PEL tumors are created using groups of 5–7 mice, and either a vehicle or drug cocktail is used to treat them. Multiple replications of every biological experiment are carried out. 30 mg/kg or 60 mg/kg of Rosiglitazone is suspended in 0.25% methylcellulose, which serves as the vehicle for the medication. PBS serves as a vehicle for the drugs Perifosine and Miltefosine, which are dissolved in the solution at a concentration of 50 mg/kg each. In order to dissolve NVP-BEZ235, the substance is combined with polyethylene glycol 300 in a 1:9 vol/vol ratio of 1-methyl-2-pyrrolidone. A dose of 40 mg/kg NVP-BEZ235 or an equivalent volume of the vehicle is given. Digital calipers are used to measure the tumor diameters, and tumor volume is computed. The tumors are removed and then fixed in formalin. With each animal treated as a random effect, statistical analyses are carried out using a linear model fit with the maximum likelihood.
Rats: There are five groups of male Sprague-Dawley rats (n=5), each weighing between 270 and 290 g. Miltefosine (MFS) is given to rats in the treatment groups as a single oral dose of 10 mg/kg as either an aqueous solution or MFS-LNCs dispersion by gastric gavage. This dosage, adjusted for rats, is equivalent to the 20 mg/kg Miltefosine dose given to mice in the preclinical study. Following administration, blood samples are taken through the orbital plexus while the patient is under anesthesia at intervals of 0.5, 1, 2, 4, 7, 10, 24, 48, 72, and 216 hours. The Eppendorf tubes contain EDTA. The next step is an immediate, 10-minute centrifugation of blood samples at 4000 rpm. While awaiting analysis, plasma samples are kept frozen and at -80°C.

[1]. Cancer Res. 1991 Feb 1;51(3):807-12.

[2]. Retrovirology. 2008 Jan 31;5:11.

[3]. Anticancer Drugs. 2003 Feb;14(2):167-73.

C21H46NO4P

407.57

407.316

C, 61.89; H, 11.38; N, 3.44; O, 15.70; P, 7.60

58066-85-6

58066-85-6

Solid powder

232-234ºC

3.58

68.4

P(=O)([O-])(OC([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H])OC([H])([H])C([H])([H])[N+](C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H]

PQLXHQMOHUQAKB-UHFFFAOYSA-N

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

hexadecyl (2-(trimethylammonio)ethyl) phosphate

HePC; Hexadecyl phosphocholine; Miltefosin C; HePC; Hexadecylphosphocholine; HDPC; Hexadecylphosphorylcholine; Miltefosinum; mpavido; Miltex; Choline Phosphate Hexadecyl Ester Hydroxide Inner Salt; hexadecylphosphocholine; Miltefosin; Miltefosina; Miltefosinum

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

配方 1 中的溶解度: 100 mg/mL (245.36 mM) in PBS (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液; 超声助溶。

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配方 2 中的溶解度: Saline: 30mg/mL

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。