Perifosine (KRX0401)   中文名称: 哌立福新

Akt (IC50 = 4.7 μM)

Perifosine 在永生化角质形成细胞 (HaCaT) 和头颈鳞状癌细胞中表现出抗增殖特性，IC50 范围为 0.6 至 8.9 M。 [1] Perifosine 诱导 G1 和 G2 细胞周期停滞，显着降低 Akt 和细胞外信号 -调节激酶 (Erk) 1/2 磷酸化水平，并以剂量依赖性方式抑制小鼠神经胶质祖细胞的生长。 [2]在 MM.1S 细胞中，periforosine (10 μM) 完全阻止 Akt 的磷酸化。[3]最近的一项研究表明 Perifosine 阻断 Akt 磷酸化，导致人肝细胞癌细胞系细胞周期停滞和凋亡。 [4]

在体内，哌立福辛和替莫唑胺的组合可抑制肿瘤的生长（PDGF 驱动的神经胶质瘤发生）。根据研究结果，哌立福辛是治疗 Akt 和 Ras-Erk 1/2 通路频繁激活的神经胶质瘤的有效药物。这表明哌立福辛可能成为临床治疗神经胶质瘤的新候选药物。 [2]与仅接受 PBS 载体治疗的对照动物相比，每天和每周口服哌立福辛可显着减少人类 MM 肿瘤的生长并提高生存率。 [3] Perifosine 可引起骨髓瘤异种移植物细胞凋亡，同时诱导血小板增多、白细胞增多，并增加小鼠骨髓和脾脏中的骨髓生成。 [5]

在 MM.1S 细胞培养过程中，可以存在或不存在哌立福辛（5 μM，6 小时）。随后，使用 IL-6（20 ng/mL，10 分钟）刺激细胞。然后使用 Akt 激酶检测试剂盒进行体外 akt 激酶检测。

培养基含有10% FCS和指定浓度的Periosine，细胞孵育48小时。 MTT 测定使用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑来测量细胞的活力。罗氏细胞增殖试剂盒I。借助96孔板读数器，测量590 nm处的吸光度。

Mice: Mice with tumors are given medication. Image-positive For 3 to 5 days, Ef-luc Ntv-a mice are given daily treatments that include intraperitoneal administration of buffer alone as a control, intraperitoneal administration of 100 mg/kg Temozolomide, oral administration of 30 mg/kg Perifosine, or a combination of Perifosine and Temozolomide. Treatments' average doses are as follows: Control, 5 (all five); Temozolomide, 3.75 (three to five); Perifosine, 3.75 (three to four); and Perifosine+Temozolomide, 3 (all three). In the control buffer solution, distilled water was combined with 5% DMSO and 1% Tween 80.
Rats: Rats are treated with Perifosine (20 mg/kg, ip, once), an Akt inhibitor, 30 min before rapamycin administration to further ascertain whether the paradoxical effect of rapamycin on S6 phosphorylation is connected to upstream signals of Akt-mTOR. Rats are euthanized 1 or 6 hours after receiving rapamycin injections.

[1]. Cancer Res . 2002 Mar 1;62(5):1401-9.

[2]. Cancer Res . 2005 Aug 15;65(16):7429-35.

[3]. Blood . 2006 May 15;107(10):4053-62.

Perifosine is a phospholipid consisting of 1,1-dimethylpiperidinium-4-yl hydrogen phosphate in which the hydrogen is replaced by a stearyl (octadecyl) group. It has a role as an EC 2.7.1.137 (phosphatidylinositol 3-kinase) inhibitor. It is a phospholipid and an ammonium betaine. It is functionally related to an octadecan-1-ol.
Perifosine is a novel alkylphospholipid with antiproliferative properties attributed to protein kinase B inhibition.
Perifosine is an orally active alkyl-phosphocholine compound with potential antineoplastic activity. Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. Perifosine has a lower gastrointestinal toxicity profile than the related agent miltefosine. (NCI04)

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Drug Indication
Investigated for use/treatment in solid tumors, multiple myeloma, leukemia (unspecified), lung cancer, and brain cancer.

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Mechanism of Action
Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis.

C25H52NO4P

461.6584

461.363

C, 65.04; H, 11.35; N, 3.03; O, 13.86; P, 6.71

157716-52-4

157716-52-4

148177

White to off-white solid powder

271-272° (dec)

5.6

68.4

0

4

20

31

454

0

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])C([H])([H])C([H])([H])[H])OC1([H])C([H])([H])C([H])([H])[N+](C([H])([H])[H])(C([H])([H])[H])C([H])([H])C1([H])[H]

SZFPYBIJACMNJV-UHFFFAOYSA-N

InChI=1S/C25H52NO4P/c1-4-5-6-7-8-9-10-11-12-13-14-15-16-17-18-19-24-29-31(27,28)30-25-20-22-26(2,3)23-21-25/h25H,4-24H2,1-3H3

1,1-dimethylpiperidin-1-ium-4-yl octadecyl phosphate.

Perifosine; KRX-0401; KRX 0401; KRX0401; NKA17; NSC639966; NSC 639966; NSC-639966; D 21266; D-21266

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)

DMSO: ~15 mg/mL (~32.5 mM)
Water: ~8 mg/mL (~17.3 mM)
Ethanol: <1 mg/mL

配方 1 中的溶解度: 50 mg/mL (108.30 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: 30%Propylene glycol, 5%Tween 80, 65% D5W: 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。