Valproic acid sodium(Synonyms: 丙戊酸钠; Sodium Valproate sodium)

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Valproic acid sodium (Synonyms: 丙戊酸钠; Sodium Valproate sodium) 纯度: ≥98.0%

Valproic acid sodium salt (Sodium Valproate) 是一种 HDAC 抑制剂,IC50 值为 0.5-2 mM,抑制 HDAC1 的活性,(IC50,400 μM),同时可诱导 HDAC2 的降解。Valproic acid sodium salt 激活 Notch1 信号并抑制小细胞肺癌 (SCLC) 细胞的增殖。Valproic acid sodium salt 可用于癫痫、双相情感障碍和偏头痛等的研究。

Valproic acid sodium(Synonyms: 丙戊酸钠; Sodium Valproate sodium)

Valproic acid sodium Chemical Structure

CAS No. : 1069-66-5

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生物活性

Valproic acid sodium salt (Sodium Valproate) is an HDAC inhibitor, with IC50 in the range of 0.5 and 2 mM, also inhibits HDAC1 (IC50, 400 μM), and induces proteasomal degradation of HDAC2. Valproic acid sodium salt activates Notch1 signaling and inhibits proliferation in small cell lung cancer (SCLC) cells. Valproic acid sodium salt is used in the treatment of epilepsy, bipolar disorder and prevention of migraine headaches.

IC50 & Target[5][6]

HDAC1

400 μM (IC50)

HDAC

0.5-2 mM (IC50)

HDAC2

 

Autophagy

 

Mitophagy

 

体外研究
(In Vitro)

Valproic acid sodium salt (Sodium Valproate) inhibits the growth dose- and time-dependently with an IC50 of appr 10 and 4 mM at 24 and 72 h, respectively. Valproic acid sodium salt significantly attenuates the activities of total, cytosol and nuclear HDACs. Valproic acid sodium salt increases the form of acetylated histone 3 in HeLa cells. Valproic acid sodium salt (1-3 mM) induces a G1 phase arrest, while 10 mM Valproic acid sodium salt significantly induces a G2/M phase arrest of cell cycle in HeLa cells. In addition, Valproic acid sodium salt increases the percentage of sub-G1 cells in HeLa cells in a dose-dependent manner at 24 h[1].
Valproic acid sodium salt inhibits the mRNA and protein expression of VEGF, VEGFR2 and bFGF. Valproic acid sodium salt inhibits the protein expression of HDAC1, increases histone H3 acetylation, and enhances the accumulation of hyperacetylated histone H3 on VEGF promoters[2].
Valproic acid sodium salt treatment results in increased levels of phosphorylated AMPK/ACC in primary mouse hepatocytes. Phosphorylation of ACC following Valproic acid sodium salt treatment is AMPK-dependent. Valproic acid sodium salt inhibits the deacetylase activity of both mouse liver nuclear extracts and human recombinant HDAC1 while of the metabolites of Valproic acid, only 2-ene-Valproic acid and 4-ene-Valproic acid diminish deacetylase activity[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

体内研究
(In Vivo)

Valproic acid sodium salt (Sodium Valproate; 500 mg/kg, i.p.) inhibits the tumor growth and angiogenesisin the mice transplanted with Kasumi-1 cells. The IR rate in the Valproic acid sodium salt group is 57.25% at the end of the experiment[2].
Valproic acid sodium salt (350 mg/kg, i.p.) demonstrates more social investigation and play fighting than control animals[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

分子量

166.19

Formula

C8H15NaO2

CAS 号

1069-66-5

中文名称

丙戊酸钠;丙戊酸钠盐;定百痉;癫扑净;抗癫灵;敌白痉;2-丙基戊酸钠

运输条件

Room temperature in continental US; may vary elsewhere.

储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

溶解性数据
In Vitro: 

H2O : 250 mg/mL (1504.30 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 6.0172 mL 30.0860 mL 60.1721 mL
5 mM 1.2034 mL 6.0172 mL 12.0344 mL
10 mM 0.6017 mL 3.0086 mL 6.0172 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效
储备液的保存方式和期限:-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。

参考文献
  • [1]. Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.

    [2]. Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.

    [3]. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.

    [4]. Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.

    [5]. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.

    [6]. Platta CS, et al. Valproic acid induces Notch1 signaling in small cell lung cancer cells. J Surg Res. 2008 Jul;148(1):31-7.

Kinase Assay
[1]

The activity of caspase-3, -8 and -9 is assessed using the caspase-3, -8 and -9 colorimetric assay kits, respectively. In brief, 1×106 cells in a 60-mm culture dish are incubated with 10 mM Valproic acid for 24 h. The cells are then washed in PBS and suspended in 5 volumes of lysis buffer provided with the kit. Protein concentrations are determined using the Bradford method. Supernatants containing 50 μg total protein are used to determine caspase-3, -8 and -9 activities. The supernatants are added to each well in 96-well microtiter plates with DEVD-pNA, IETD-pNA or LEHD-pNA as caspase-3, -8 and -9 substrates and the plates are incubated at 37°C for 1 h. The optical density of each well is measured at 405 nm using a microplate reader. The activity of caspase-3, -8 and -9 is expressed in arbitrary absorbance units.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

In brief, 5×105 cells are seeded in 96-well microtiter plates for MTT assays. After exposure to the designated doses of Valproic acid for the indicated times, MTT solution [20 mL: 2 mg/mL in phosphate-buffered saline (PBS)] is added to each well of the 96-well plates. The plates are additionally incubated for 3 h at 37°C. Medium is withdrawn from the plates by pipetting and 200 mL DMSO is added to each well to solubilize the formazan crystals. The optical density is measured at 570 nm using a microplate reader.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Splenectomies are performed on the BALB/c nude mice. One week after the splenectomies, the mice receiv whole body irradiation with 137Cs at a dose of 4 Gy. At 48-72 h post-irradiation, the mice are subcutaneously implanted with Kasumi-1 cells (2×107 cells/mouse with 0.15-0.2 mL) in the right axillary region. The mice are randomLy assigned to two groups, the Valproic acid (n=6) and control (n=6) groups. When the tumors are appr 200 mm3 in size at appr 10 days post-implantation, 0.2 mL Valproic acid (500 mg/kg body weight) or 0.2 mL saline is injected intraperitoneally every day. Valproic acid is dissolved in saline at a concentration of 25 mg/mL. The longest diameter (a) and the shortest diameter (b) of the tumor are measured every three days, and the tumor volume (TV) is calculated according to the following formula: TV=1/2×a×b2. Following two weeks of injections, the mice are sacrificed by cervical dislocation and the tumor masses are removed for the following experiments.

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

参考文献
  • [1]. Han BR, et al. Valproic acid inhibits the growth of HeLa cervical cancer cells via caspase-dependent apoptosis. Oncol Rep. 2013 Dec;30(6):2999-3005.

    [2]. Valproic acid, et al. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem. 2001 Sep 28;276(39):36734-41.

    [3]. Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.

    [4]. Cohen OS, et al. Acute prenatal exposure to a moderate dose of valproic acid increases social behavior and alters gene expression in rats. Int J Dev Neurosci. 2013 Dec;31(8):740-50.

    [5]. Avery LB, et al. Valproic Acid Is a Novel Activator of AMP-Activated Protein Kinase and Decreases Liver Mass, Hepatic Fat Accumulation, and Serum Glucose in Obese Mice. Mol Pharmacol. 2014 Jan;85(1):1-10.

    [6]. Platta CS, et al. Valproic acid induces Notch1 signaling in small cell lung cancer cells. J Surg Res. 2008 Jul;148(1):31-7.

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