{[(1,1-dimethylpiperidin-1-ium-4-yl)oxy](octadecyloxy)phosphoryl}-$l^{3}-oxidanediide

• ChemBase编号: 72598
• 分子式: C25H52NO4P-
• 平均质量: 461.658441
• 单一同位素质量: 461.36339578
• SMILES: C1C[N+](CCC1OP(=O)([O-2])OCCCCCCCCCCCCCCCCCC)(C)C
• Canonical SMILES: CCCCCCCCCCCCCCCCCCOP(=O)(OC1CC[N+](CC1)(C)C)[O-2]
• 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/q-1
• InChIKey: LHJQEUOALPPIHG-UHFFFAOYSA-N

名称和登记号

名称

• IUPAC标准名: {[(1,1-dimethylpiperidin-1-ium-4-yl)oxy](octadecyloxy)phosphoryl}-$l^{3}-oxidanediide
• IUPAC传统名: [(1,1-dimethylpiperidin-1-ium-4-yl)oxy(octadecyloxy)phosphoryl]-$l^{3}-oxidanediide
• 别名: KRX-0401; NSC 639966; Perifosine

登记号

• CAS号: 157716-52-4
• PubChem SID: 162037523
• PubChem CID: 0

理论计算性质

• 质子受体: 0
• 质子供体: 0
• 摩尔折射率: 142.1471 cm^3
• 极化表面积: 58.59 Å^2
• 可自由旋转的化学键: 20
• 里宾斯基五规则: false

分子性质

理化性质

• 溶解度: H2O

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: Akt; PI3K

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1037

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

参考文献

• 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