Molecular Weight (MW)

461.66

Formula

C25H52NO4P

CAS No.

157716-52-4

Storage

-20℃ for 3 years in powder form

-80℃ for 2 years in solvent

Solubility (In vitro)

DMSO: 15 mg/mL (32.5 mM)

Water: 8 mg/mL (17.3 mM)

Ethanol: <1 mg/mL

Solubility (In vivo)

30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL

Other info

Synonym: KRX-0401; KRX 0401; KRX0401; NKA17; NSC639966; NSC 639966; NSC-639966; D 21266; D-21266

Chemical Name: 1,1-dimethylpiperidin-1-ium-4-yl octadecyl phosphate.

InChi Key: SZFPYBIJACMNJV-UHFFFAOYSA-N

InChi Code: 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

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

In Vitro

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.

Cell Assay: Cells (Human glioma cell lines) 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.

Perifosine develops anti-proliferative properties with IC50 of 0.6-8.9 μM in immortalized keratinocytes (HaCaT), and head and neck squamous carcinoma cells. 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. Perifosine (10 μM) completely inhibits the phosphorylation of Akt in MM.1S cells. A recent study demonstrates Perifosine induces cell cycle arrest and apoptosis in human hepatocellular carcinoma cell lines by blockade of Akt phosphorylation.

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. 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. Perifosine induces thrombocytosis and leukocytosis and increases myelopoiesis in murine marrow and spleen, whereas it causes apoptosis in myeloma xenografts.

Animal model

MM.1S MM cells are inoculated subcutaneously in the right flank of Beige-nude-xid (BNX) mice (5 to 6 weeks old).

Formulation & Dosage

Dissolved in 0.9% NaCl solution; 36 mg/kg; oral administration

References

[1] Hideshima T, et al. Blood, 2006, 107(10), 4053-4062.; [2] Vyomesh Patel, et al. Cancer Res, 2002, 62(5), 1401-1409