N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide

• ChemBase编号: 72707
• 分子式: C22H20N2O5S
• 平均质量: 424.4696
• 单一同位素质量: 424.10929275
• SMILES: c1cccc(c1N(S(=O)(=O)c1ccc(cc1)OC)C(=O)C)/C=C/c1cc[n+](cc1)[O-]
• Canonical SMILES: COc1ccc(cc1)S(=O)(=O)N(c1ccccc1/C=C/c1cc[n+](cc1)[O-])C(=O)C
• InChI: InChI=1S/C22H20N2O5S/c1-17(25)24(30(27,28)21-11-9-20(29-2)10-12-21)22-6-4-3-5-19(22)8-7-18-13-15-23(26)16-14-18/h3-16H,1-2H3/b8-7+
• InChIKey: OCKHRKSTDPOHEN-BQYQJAHWSA-N

名称和登记号

名称

• IUPAC标准名: N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide
• IUPAC传统名: N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide
• 别名: IVX-214; HMN-214

登记号

• CAS号: 173529-46-9
• PubChem SID: 162037628
• PubChem CID: 9888590

理论计算性质

• 质子受体: 5
• 质子供体: 0
• LogD (pH = 5.5): 2.153845
• LogD (pH = 7.4): 2.1538596
• Log P: 2.1538599
• 摩尔折射率: 115.9067 cm^3
• 极化性: 44.205864 Å^3
• 极化表面积: 89.14 Å^2
• 可自由旋转的化学键: 5
• 里宾斯基五规则: true

分子性质

理化性质

• 溶解度: DMSO

安全信息

• 保存条件: -20°C

药理学性质

• 作用靶点: PLK

产品相关信息

• 成盐信息: Free Base

详细说明

Selleck Chemicals - S1485

Research Area

• Description: Cancer

Biological Activity

• Description: HMN-214 (IVX-214) is a potent inhibitor of Polo-like kinase (Plk)1 with IC50 of 118 nM.
• Targets: Polo-like kinase (Plk)1
• IC50: 118 nM ^[1]
• In Vitro: HMN-214 is an oral prodrug that is rapidly converted to HMN-176. The in vitro data of HMN-214 are scarce. However, HMN-176, active metabolite of HMN-214, shows potent and broad-spectrumanti-tumor activity against various cancer cells, including HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr, with a mean IC50 value of 118 nM. HMN-176 is also cytotoxic to drug-resistant human and murine cell lines, including P388/CDDP, P388/VCR, K2/CDDP, and K2/VP-16, with IC50 values ranging from 143 nM–265 nM. In HeLa cells, HMN-176 (3 μM) blocks cell cycle at G2/M phase. ^[1]In Doxorubicin-resistant K2/ARS cells, HMN-176 inhibits cell growth with an IC50 value of 2 μM. HMN-176 (3 μM) down-regulates the expression of the multidrug resistance gene (MDR1), due to the disturbance of NF-Y transcription factor binding to the MDR1 promoter. ^[2]In human RPE1 and CFPAC-1 cells, HMN-176 (2.5 μM) delays satisfaction of the spindle assembly checkpoint. HMN-176 (250 nM–2.5 μM) inhibits meiotic spindle assembly and aster formationin Spisula oocytes. HMN-176 (2.5 μM) also inhibits aster microtubule formation from human centrosomes. These results indicate that the anti-tumor activity of HMN-176 is at least partially via disrupting centrosome-mediated MT assembly during mitosis. ^[3]
• In Vivo: HMN-214 is an oral pro-drug of HMN-176 with improved oral absorption. HMN-214 (30 mg/kg) triggers no obvious neurotoxicity in mice. In mouse xenograft model of PC-3, A549, and WiDr cells, HMN-214 (10 mg/kg–20 mg/kg) inhibits tumor growth. ^[1]In nude mice model bearing multidrug-resistant KB-A.1 cells, HMN-214 (10 mg/kg–20 mg/kg) significantly suppresses MDR1 mRNA expression. ^[2]

Protocol

• Protocol: Cell Assay ^[1]
• Cell Lines: HeLa, PC-3, DU-145, MIAPaCa-2, U937, MCF-7, A549, and WiDr cells
• Concentrations: 0–10 μM, dissolved in DMSO
• Incubation Time: 72 hours
• Methods: Cells are seeded into a 96-well microplate at a density of 3 × 10^3–1 × 10^4 cells/well. Dilutions of HMN-214 or HMN-176 are added the next day and the plate is incubated for 72 hours. The inhibition of growth is measured by the MTT assay and IC50 values are then obtained.
• Protocol: Animal Study ^[1]
• Animal Models: Male BALB/c nude mice bearing xenografts of PC-3, A549, and WiDr cells
• Formulation: Dissolved in 0.5% methylcellulose
• Doses: 10 mg/kg–20 mg/kg
• Administration: Oral gavage on a QD × 28 schedule

References

• References: [1] Takagi M, et al. Invest New Drugs, 2003, 21(4), 387-399.
• References: [2] Tanaka H, et al. Cancer Res, 2003, 63(20), 6942-6947.
• References: [3] DiMaio MA, et al. Mol Cancer Ther, 2009, 8(3), 592-601.

参考文献

• Takagi M, et al. Invest New Drugs, 2003, 21(4), 387-399.
• Tanaka H, et al. Cancer Res, 2003, 63(20), 6942-6947.
• DiMaio MA, et al. Mol Cancer Ther, 2009, 8(3), 592-601.