Perifosine

• Catalog No.: S1037
• CAS Number: 157716-52-4
• M. F.: C25H52NO4P-
• M. W.: 461.658441
• Storage: -20°C

SYNONYMS

• IUPAC name: {[(1,1-dimethylpiperidin-1-ium-4-yl)oxy](octadecyloxy)phosphoryl}-$l^{3}-oxidanediide
• IUPAC Traditional name: [(1,1-dimethylpiperidin-1-ium-4-yl)oxy(octadecyloxy)phosphoryl]-$l^{3}-oxidanediide
• Synonyms: NSC 639966; KRX-0401

DATABASE IDS

• CAS Number: 157716-52-4

PROPERTIES

• Target: Akt
• Target: PI3K
• Salt Data: Free Base
• Solubility: H2O
• Storage Condition: -20°C

DETAILS

Description (English)

Biological Activity

• Description: Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM.
• Targets: AKT
• IC50: 4.7 μM ^[1]
• In Vitro: 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. ^[2] Perifosine develops anti-proliferative properties with an IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. ^[1] Perifosine (10 μM) completely inhibits the phosphorylation of Akt in MM.1S cells in a time-dependent fashion.^[3] A recent study demonstrates Perifosine induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cell lines by blockade of Akt phosphorylation. ^[4]
• In Vivo: Perifosine combining with temozolomide reduces tumor proliferation (a PDGF-driven gliomagenesis) in vivo. The results indicate that Perifosine is an effective drug in gliomas in which Akt and Ras-Erk 1/2 pathways are frequently activated, and may be new candidate for glima treatment in the clinic. ^[2] Both oral daily and weekly administration of Perifosine significantly reduce human MM tumor growth and increase survival, compared with control animals treated with PBS vehicle only. ^[3] Perifosine induced thrombocytosis and leukocytosis and increased myelopoiesis in murine marrow and spleen, whereas it causes apoptosis in myeloma xenografts. ^[5]
• Clinical Trials: Perifosine is undergoing its Phase III clinical trials for the treatment of refractory multiple myeloma, in combination with a Placebo, and is in Phase II trials for several other cancers.

Protocol

• Protocol: Kinase Assay ^[3]
• Akt kinase assay: MM.1S cells are cultured in the presence or absence of perifosine (5 μM, 6 hours) and then stimulated with IL-6 (20 ng/mL, 10 minutes). In vitro akt kinase assay is then carried out using the Akt Kinase Assay Kit.
• Protocol: Cell Assay ^[2]
• Cell Lines: Human glioma cell lines
• Concentrations: 0, 15, 30 and 45 μM
• Incubation Time: 48 hours
• Methods: Cells are incubated in the medium with 10% FCS for 48 hours with indicated concentration of Periosine. Cell viability is determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. (Cell Proliferation Kit I; Roche). The absorbance at 590 nm is recorded using the 96-well plate reader.
• Protocol: Animal Study ^[3]
• Animal Models: MM.1S MM cells are inoculated subcutaneously in the right flank of Beige-nude-xid (BNX) mice (5 to 6 weeks old).
• Formulation: 0.9% NaCl solution
• Doses: 250 mg/kg/wk or 36 mg/kg/d
• Administration: Oral gavage

References

• References: [1] Vyomesh Patel, et al. Cancer Res, 2002, 62(5), 1401-1409
• References: [2] Momota H, et al. Cancer Res, 2005, 65(16), 7429-7435.
• References: [3] Hideshima T, et al. Blood, 2006, 107(10), 4053-4062.
• References: [4] Fei HR, et al. Cytotechnology, 2010, 62(5), 449-460
• References: [5] Catley L, et al. Exp Hematol, 2007, 32(7), 1038-1046

REFERENCES

• Vyomesh Patel, et al. Cancer Res, 2002, 62(5), 1401-1409
• Momota H, et al. Cancer Res, 2005, 65(16), 7429-7435.
• Hideshima T, et al. Blood, 2006, 107(10), 4053-4062.
• Fei HR, et al. Cytotechnology, 2010, 62(5), 449-460
• Catley L, et al. Exp Hematol, 2007, 32(7), 1038-1046