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Cat. No. Name Size Price Add Cart
KI0230Perifosine5 mg$140
Perifosine10 mg$218
Perifosine25 mg$400
Perifosine50 mg$720

Chemical Characteristic

Product NamePerifosine
SynonymsNSC 639966,KRX-0401
CAS No.157716-52-4
Molecular Weight 461.66
FormulaC25H52NO4P
Chemical Name(1,1-Dimethylpiperidin-1-ium-4-yl) octadecyl phosphate
SmilesP(=O)(OCCCCCCCCCCCCCCCCCC)(OC1CC[N](CC1)(C)C)O
Chemical Structure

Biological activities

Perifosine is a synthetic novel alkylphospholipid (ALP), which targets cell membranes, inhibits Akt activation with an IC50 of 0.6 µM, and induces apoptosis in PC-3 prostate carcinoma cells, epithelial carcinoma cell line A431, and HeLa cells. Perifosine significantly inhibits growth of MM.1S, MM.1R, U266, INA-6, RPMI8226, RPMI-LR5, RPMI-Dox40, OPM1, and OPM2 cells at 48 hours in a dose-dependent fashion, with IC50 of 1 to 12.5 µM. Perifosine induces significant cytotoxicity in both multiple myeloma (MM) cell lines and patient MM cells resistant to conventional therapeutic agents. Perifosine triggers c-Jun N-terminal kinase (JNK) activation, followed by caspase-8/9 and poly (ADP)-ribose polymerase cleavage. Perifosine increases phosphorylation of extracellular signal-related kinase (ERK). Furthermore, perifosine augments dexamethasone, doxorubicin, melphalan, and bortezomib-induced MM cell cytotoxicity.[1] Perifosine strongly reduces phosphorylation levels of Akt and extracellular signal-regulated kinase (Erk) 1/2, induces cell cycle arrest in G1 and G2, and causes dose-dependent growth inhibition of mouse glial progenitors in which Akt and/or Ras-Erk 1/2 pathways are activated. [2] Perifosine causes cell cycle arrest with induction of p21WAF1/CIP1 in a p53-independent fashion. Perifosine causes dose-dependent inhibition of protein kinase B/Akt phosphorylation and thus activation at concentrations causing growth inhibition of PC-3 prostate carcinoma cells. Perifosine decreases the plasma membrane localization of Akt. [3] In vivo, perifosine inhibits human MM cell growth and prolongs host survival in a murine model of human MM, associated with inhibition of Akt in tumor cells. [1] Combination therapy of perifosine and temozolomide reduces tumor proliferation. [2]

Protocols

Perifosine stock solutions are prepared by dissolving perifosine in PBS for cell culture, and in 0.9% NaCl solution for mouse treatment both at 25 mM concentration. [2]

References

[1] Hideshima T, et al. Perifosine, an oral bioactive novel alkylphospholipid, inhibits Akt and induces in vitro and in vivo cytotoxicity in human multiple myeloma cells. Blood. 2006, 107(10): 4053-4062
[2] 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.
[3] Kondapaka SB, et al. Perifosine, a novel alkylphospholipid, inhibits protein kinase B activation. Mol Cancer Ther. 2003, 2(11): 1093-1103.

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