| Identification | Back Directory | [Name]
Perifosine (KRX-0401) | [CAS]
157716-52-4 | [Synonyms]
D21266
D-21266
KRX0401
D 21266
KRX-0401
KRX 0401
NSC 639966
Perifosine
KRX-0401, NKA17
Perifosine, >=98%
Perifosine,D 21266
Perifosine(KRX-0401)
Perifosine (NSC-639966)
Octadecyl-(1,1-dimethyl-4-piperidylio) phosphate
1,1-diMethylpiperidiniuM-4-yl octadecyl phosphate
(1,1-Dimethylpiperidin-1-ium-4-yl) octadecyl phosphate
D-21266
octadecyl-(N,N-diMethyl-piperidino-4-yl)-phosphate
4-((Hydroxy(octadecyloxy)phosphinyl)oxy)-1,1-dimethylpiperidinium inner salt
4-[[Hydroxy(octadecycloxy)phosphinyl]oxy]-1,1-diMethylpiperidiniuM inner salt
Piperidinium, 4-[[hydroxy(octadecyloxy)phosphinyl]oxy]-1,1-dimethyl-, inner salt | [EINECS(EC#)]
690-653-3 | [Molecular Formula]
C25H52NO4P | [MDL Number]
MFCD00927554 | [MOL File]
157716-52-4.mol | [Molecular Weight]
461.663 |
| Chemical Properties | Back Directory | [Melting point ]
271-272° (dec) | [storage temp. ]
?20°C | [solubility ]
H2O: soluble10mg/mL, clear | [form ]
powder | [color ]
white to beige | [InChIKey]
SZFPYBIJACMNJV-UHFFFAOYSA-N | [CAS DataBase Reference]
157716-52-4 |
| Hazard Information | Back Directory | [Uses]
An alkylphospholipid which inhibits Akt activation and the anti-apoptotic MAPK pathway. | [Uses]
Antineoplastic. | [Uses]
It acts as an Akt inhibitor and a PI3K inhibitor, and is a drug candidate being developed for a variety of cancer indications.
| [Definition]
ChEBI: A phospholipid consisting of 1,1-dimethylpiperidinium-4-yl hydrogen phosphate in which the hydrogen is replaced by a stearyl (octadecyl) group. | [Biological Activity]
perifosine is an inhibitor of akt [1].perifosine is a synthetic antitumor alkylphospholipid. it induces cell apoptosis through inhibiting the activity of akt. perifosine shows antitumor activity in various cell lines including nsclc, mm, epithelial carcinoma, prostate carcinoma and leukemia cells. in h460 cells, perifosine decreased cell survival and induced apoptosis with ic50 values of 1μm and 10 μm, respectively. the treatment of perifosine was also found to induce cleavage of caspase-8, caspase-9, caspase-3 and parp in this cell line. in mm.1s cells, perifosine induced sub-g1 phase population increase from 15% to 57% at 10 μm and induced cleavage of caspase-8, caspase-9 and parp in a dose-dependent manner. in mice inoculated with mm.1s cells, oral administration of perifosine significantly reduced mm tumor growth and increased survival [1, 2]. | [Biochem/physiol Actions]
Perifosine (octadecyl-(1,1-dimethyl-4-piperidylio)) is an antitumor compound. It acts at lipid rafts and stops lysosomal accumulation and mTORC1 (mammalian target of rapamycin complex 1) signaling. This drug exhibits significant antiproliferative activity in vitro and in vivo in various human cancer model systems. | [Enzyme inhibitor]
This novel Akt signal-transduction pathway inhibitor (F.Wt. = 461.66; CAS
157716-52-4; Solubility (25°C) : <1 mg/mL DMSO, 8 mg/mL Water), also
known as KRX-0401 and 1,1-dimethylpiperidinium-4-yl octadecyl
phosphate (zwitterion), inhibits Akt protein kinases, IC50 = 5 μM. Perifosine
strongly inhibits Akt and extracellular signal-regulated kinase (Erk) 1/2,
inducing cell cycle arrest in G1 and G2, as well as dose-dependent growth
inhibition of mouse glial progenitors. Perifosine (10 μM) completely
inhibits Akt in MM.1S cells and induces cell cycle arrest and apoptosis
in human hepatocellular carcinoma cell lines, again by inhibiting Akt
phosphorylation. Note: Perifosine is related structurally to miltefosine.
| [target]
AKT | [storage]
Store at -20°C | [References]
[1] elrod h a, lin y d, yue p, et al. the alkylphospholipid perifosine induces apoptosis of human lung cancer cells requiring inhibition of akt and activation of the extrinsic apoptotic pathway. molecular cancer therapeutics, 2007, 6(7): 2029-2038.
[2] hideshima t, catley l, yasui h, 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. |
| Questions And Answer | Back Directory | [Description]
Perifosine (KRX-0401) is a novel Akt inhibitor with IC50 of 4.7 μM in MM.1S cells, targets pleckstrin homology domain of Akt. Phase 3. | [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.
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