Perifosine is an oral Akt inhibitor which inhibits proliferation of different tumor cell lines with IC₅₀s of 0.6-8.9 μM.

The IC₅₀ for growth of Ntv-a/LacZ cell lines is determined by MTT assay. When the cells are cultured for 48 hours in 10% FCS-supplemented media, the IC₅₀ for cells with constitutively active PDGF, Ras, or Akt signaling is similar and found to be ~45 μM^[1].Perifosine, a oral-bioavailable alkylphospholipid (ALK), on the cell cycle kinetics of immortalized keratinocytes (HaCaT) as well as head and neck squamous carcinoma cells. Proliferation is assessed by the incorporation of [³H]thymidine into cellular DNA. Exposure to Perifosine (0.1-30 μM) for 24 h results in a dose-dependent inhibition of [³H]thymidine uptake in all cell lines tested. The IC₅₀s for growth are between 0.6 and 8.9 μM, reaching IC₈₀s of ~10 μM. Perifosine blocks cell cycle progression of head and neck squamous carcinoma cells at G₁-S and G₂-M by inducing p21^WAF1, irrespective of p53 function, and may be exploited clinically because the majority of human malignancies harbor p53 mutations. Perifosine (20 μM) induces both G₁-S and G₂-M cell cycle arrest, together with p21^WAF1 expression in both p53 wild-type and p53^-/- clones^[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mice are identified with tumors by bioluminescence imaging and either treated them with 100 mg/kg Temozolomide, or 30 mg/kg Perifosine, or a combination with 100 mg/kg Temozolomide and 30 mg/kg Perifosine (Temozolomide+Perifosine) for 3 to 5 days. The mice are sacrificed and tumors analyzed histologically for cell proliferation by Ki-67 immunostaining. Ki-67 staining index is significantly reduced in mice treated with either Temozolomide (Ki-67 staining index=5.5±1.2%, n=4, P=0.0019) or Perifosine (Ki-67 staining index=3.2±1.1%, n=3, P=0.001) compared with Control, demonstrating the inhibitory effect on proliferation. Most importantly, the tumors treated with Temozolomide+Perifosine have the lowest Ki-67 staining index (1.7±1.2%, n=3, P=0.0005). The additional treatment with Perifosine results in a significantly lower proliferation rate than Temozolomide alone (P=0.0087)^[1]. Perifosine markedly decreases p-Akt from 10 min to 24 hours and subsequently, moderately decreased p-S6 from 1h to 24 h after injection^[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

461.66

C₂₅H₅₂NO₄P

157716-52-4

Solid

White to off-white

[O-]P(OC1CC[N+](C)(CC1)C)(OCCCCCCCCCCCCCCCCCC)=O

Room temperature in continental US; may vary elsewhere.

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.

• [1]. Momota H, et al. Perifosine inhibits multiple signaling pathways in glial progenitors and cooperates with temozolomide to arrest cell proliferation in gliomas in vivo. Cancer Res, 2005, 65(16), 7429-7435.  [Content Brief]

  [2]. Vyomesh Patel, et al. Perifosine, a novel alkylphospholipid, induces p21(WAF1) expression in squamous carcinoma cells through a p53-independent pathway, leading to loss in cyclin-dependent kinase activity and cell cycle arrest. Cancer Res, 2002, 62(5), 14  [Content Brief]

  [3]. Chen L, et al. Rapamycin has paradoxical effects on S6 phosphorylation in rats with and without seizures. Epilepsia. 2012 Nov;53(11):2026-33.  [Content Brief]