Perifosine

Perifosine is an orally active alkyl-phosphocholine compound with potential antineoplastic activity. Targeting cellular membranes, perifosine modulates membrane permeability, membrane lipid composition, phospholipid metabolism, and mitogenic signal transduction, resulting in cell differentiation and inhibition of cell growth. This agent also inhibits the anti-apoptotic mitogen-activated protein kinase (MAPK) pathway and modulates the balance between the MAPK and pro-apoptotic stress-activated protein kinase (SAPK/JNK) pathways, thereby inducing apoptosis. Perifosine has a lower gastrointestinal toxicity profile than the related agent miltefosine.

Product information

CAS Number: 157716-52-4

Molecular Weight: 461.66

Formula: C25H52NO4P

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.

Smiles: CCCCCCCCCCCCCCCCCCOP([O-])(=O)OC1CC[N+](C)(C)CC1

InChiKey: SZFPYBIJACMNJV-UHFFFAOYSA-N

InChi: 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

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: Water: 8 mg/mL(17.32 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

References:

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

Products are for research use only. Not for human use.