生物活性

Perifosine is a synthetic antitumor alkylphospholipid. It induces cell apoptosis through inhibiting the activity of Akt. Perifosine shows antitumor activity in various cell lines including NSCLC, MM, epithelial carcinoma, prostate carcinoma and leukemia cells. In H460 cells, perifosine decreased cell survival and induced apoptosis with IC50 values of 1μM and 10 μM, respectively. The treatment of perifosine was also found to induce cleavage of caspase-8, caspase-9, caspase-3 and PARP in this cell line. In MM.1S cells, perifosine induced sub-G1 phase population increase from 15% to 57% at 10 μM and induced cleavage of caspase-8, caspase-9 and PARP in a dose-dependent manner. In mice inoculated with MM.1S cells, oral administration of perifosine significantly reduced MM tumor growth and increased survival.

体外研究

体内研究

30% Propylene glycol, 5% Tween 80, 65% D5W(5%葡萄糖水溶液)

激酶实验

细胞实验

0, 15, 30，45 μM

动物实验

250 mg/kg/wk或者36 mg/kg/d 口服

不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）

例如，已知某工具药用于小鼠的剂量为88 mg/kg , 则用于大鼠的剂量换算方法：将88 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到该药物用于大鼠的等效剂量44 mg/kg。

参考文献

[1] Vyomesh Patel, et al. Cancer Res, 2002, 62(5), 1401-1409.
[2] Fu et al (2009) Perifosine inhibits mammalian target of rapamycin signaling through facilitating degradation of major components in the mTOR axis and induces autophagy. Cancer Res. 69 8967.
[3] Tazzari et al (2008) Synergistic proapoptotic activity of recombinant TRAIL plus the Akt inhibitor Perifosine in acute myelogenous leukemia cells. Cancer Res. 68 9394.
[4] Delgado-Ramírez et al (2016) Modulation of the voltage-gated potassium channel Kv2.1 by the anti-tumor alkylphospholipid perifosine. Pharmacol Rep. 68 457.

体内溶解度

Clinical Trial Information ( data from http://clinicaltrials.gov )

注：以上所有数据均来自公开文献，并不保证对所有实验均有效，数据仅供参考。

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