物质信息

ID:73375

名称和标识
IUPAC标准名
N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide
别名
IVX-214HMN-214
IUPAC传统名
N-(4-methoxybenzenesulfonyl)-N-{2-[(E)-2-(1-oxo-1$l^{5}-pyridin-4-yl)ethenyl]phenyl}acetamide
数据登录号
化合物性质
理化性质
溶解度
DMSO
药理学性质
作用靶点
PLK
产品相关信息
成盐信息
Free Base
安全信息
保存条件
-20°C
描述信息
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]
Clinical Trials
Features
Protocol
Kinase Assay []
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 × 103–1 × 104 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.
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
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参考文献
• Tanaka H, et al. Cancer Res, 2003, 63(20), 6942-6947.
• DiMaio MA, et al. Mol Cancer Ther, 2009, 8(3), 592-601.
• Takagi M, et al. Invest New Drugs, 2003, 21(4), 387-399.
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