Perifosine (KRX-0401)

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Biological Activity

Description	Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM, targets pleckstrin homology domain of Akt. Phase 2.
Targets	AKT
IC50	4.7 μM [1]
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. [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. [2] Perifosine (10 μM) completely inhibits the phosphorylation of Akt in MM.1S cells. [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 induces thrombocytosis and leukocytosis and increases myelopoiesis in murine marrow and spleen, whereas it causes apoptosis in myeloma xenografts.[5]
Features

Protocol(Only for Reference)

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.

Cell Assay: ^[2]

Cell lines	Human glioma cell lines
Concentrations	0, 15, 30 and 45 μM
Incubation Time	48 hours
Method	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.

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).
Dosages	250 mg/kg/wk or 36 mg/kg/d
Administration	Oral gavage
Solubility	30% propylene glycol, 5% Tween 80, 65% D5W, 30 mg/mL

1

References

Clinical Trial Information( data from http://clinicaltrials.gov)

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01049841	Active, not recruiting	Pediatric Solid Tumors	Memorial Sloan-Kettering Cancer Center|University of Wisconsin, Madison|Duke University|NATL COMP CA NETWORK|Pfizer|Aeterna Zentaris GmbH	2010-01	Phase 1
NCT01051557	Active, not recruiting	Adult Anaplastic Astrocytoma|Adult Anaplastic Oligodendroglioma|Adult Diffuse Astrocytoma|Adult Giant Cell Glioblastoma|Adult Glioblastoma etc.	National Cancer Institute (NCI)	2010-01	Phase 1|Phase 2
NCT01097018	Completed	Colorectal Cancer	AEterna Zentaris	2010-04	Phase 3
NCT01224730	Active, not recruiting	Cancer	AEterna Zentaris	2012-01	Phase 1
NCT01555281	Recruiting	Multiple Myeloma	Swiss Group for Clinical Cancer Research	2012-04	Phase 1|Phase 2

Chemical Information

Download Perifosine (KRX-0401) SDF

Chemical Name	Piperidinium, 4-[[hydroxy(octadecyloxy)phosphinyl]oxy]-1,1-dimethyl-, inner salt

Customer Reviews (14)

Click to enlarge	Rating
	Source	Mol Cell Proteomics, 2012, 11(12), 1898-1912 . Perifosine (KRX-0401) purchased from Selleck
	Method	Western Blot
	Cell Lines	NB4 cells
	Concentrations	25 μM
	Incubation Time	30 min
	Results	In these experiments, the presence of MLN9708 caused an accumulation of LAT2 after ODPC (Fig. B)or perifosine (Fig. C) treatment, confirming that LAT2 is degraded by proteasomes after treatment with APL.

Product Citations (25)

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  NVP-BEZ235 alone and in combination in mantle cell lymphoma: an effective therapeutic strategy. [Ying H, et al. Cell 2012;149(3):656-70]

  
  PubMed: 22920938


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  Phosphorylation of EZH2 activates STAT3 signaling via STAT3 methylation and promotes tumorigenicity of glioblastoma stem-like cells. [Kim E, et al. Cancer Cell 2013;23(6):839-52]

  
  PubMed: 23684459


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  CD81 Is Essential for the Re-entry of Hematopoietic Stem Cells to Quiescence following Stress-Induced Proliferation Via Deactivation of the Akt Pathway. [Lin KK, et al. PLoS Biol 2011;9(9):e1001148]

  
  PubMed: 21931533