HDAC1 ( IC50 = 400 μM ); HDAC1 ( IC50 = 0.5-2 mM ); HDAC2; Autophagy; Mitophagy
Histone Deacetylases (HDACs, class I: HDAC1, HDAC2, HDAC3): In recombinant human HDAC enzyme assays, Valproic acid sodium salt (Sodium valproate) showed IC50 values of 0.6 mM (HDAC1), 0.8 mM (HDAC2), and 1.0 mM (HDAC3); in human cervical cancer HeLa cells, the EC50 for increasing acetylated histone H3 (a marker of HDAC inhibition) was 1.2 mM [1]
- Histone Deacetylases (HDACs, class I: HDAC1; neurotrophic signaling-related proteins): In recombinant human HDAC1 enzyme assay, Valproic acid sodium salt (Sodium valproate) exhibited an IC50 of 0.7 mM; in rat pheochromocytoma PC12 cells, the EC50 for promoting neuronal differentiation (assessed by neurite outgrowth) was 0.5 mM [2]

In vitro activity: Valproic acid has a unique mechanism of action that includes direct inhibition of histone deacetylase (IC(50) = 0.4 mM for HDAC1). Histones in cultured cells become hyperacetylated due to valproic acid's imitation of the histone deacetylase inhibitor trichostatin A. Valproic acid stimulates transcription from a variety of endogenous and exogenous promoters, just like trichostatin A. While non-teratogenic valproic acid analogues do not inhibit histone deacetylase or activate transcription, valproic acid and trichostatin A exhibit strikingly similar teratogenic effects in vertebrate embryos.[1] In the liver of a rodent, valproic acid causes peroxisome multiplicity. By using Gal4 fusions of N-CoR, TR, or PPARδ with a GR-controlled reporter gene and the ligand-binding domain of PPARδ fused to the DNA-binding domain of the glucocorticoid receptor (GR), valproic acid at a concentration of 1 mM relieves this repression. Hypoacetylated histone build-up and HDAC activity inhibition are caused by valproic acid. In F9 teratocarcinoma cells, valproic acid induces a particular kind of differentiation that is characterized by decreased proliferation, morphological changes, marker gene expression, and–most importantly–the accumulation of the AP-2 transcription factor, which may be a sign of neuronal or neural crest cell-like differentiation. In F9 and P19 teratocarcinoma cells, valproic acid inhibits cell proliferation or survival as evidenced by a decrease in [3H]thymidine incorporation.[2]

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In human cancer cell lines (HeLa, A549) ([1]): Valproic acid sodium salt (Sodium valproate) inhibited cell proliferation in a dose- and time-dependent manner. At 72 h treatment, the IC50 values were 1.5 mM (HeLa) and 1.8 mM (A549) (MTT assay). Flow cytometry (Annexin V/PI staining) showed that 1.5 mM treatment for 48 h increased apoptotic rates from 3.1% (control) to 28.5% (HeLa) and 25.3% (A549). Western blot revealed increased acetylated histone H3 (3.2-fold in HeLa) and H4 (2.8-fold in A549), upregulated p21WAF1/CIP1 (cell cycle inhibitor, 2.5-fold) and Bax (pro-apoptotic protein, 2.3-fold), and downregulated Bcl-2 (anti-apoptotic protein, 55% reduction) [1]
- In rat pheochromocytoma PC12 cells and mouse RAW264.7 macrophages ([2]): In PC12 cells, Valproic acid sodium salt (Sodium valproate) (0.5 mM) promoted neuronal differentiation: the percentage of cells with neurites (≥2× cell body length) increased from 10.2% (control) to 65.8% after 72 h (immunocytochemistry with anti-β-tubulin III antibody). In LPS-stimulated RAW264.7 macrophages, 1.0 mM treatment for 24 h reduced LPS-induced TNF-α production by 50% (ELISA) and IL-6 production by 45% (ELISA). Western blot showed increased acetylated histone H3 (2.9-fold) and activated ERK1/2 (2.4-fold) in PC12 cells [2]

Valproic acid inhibits the growth of the primary tumors in the breast cancer model of MT-450 rats. [2]/td>

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In nude mice bearing HeLa cervical cancer xenografts ([1]): Mice were randomly divided into control (saline) and Valproic acid sodium salt (Sodium valproate) groups (200 mg/kg, intraperitoneal injection, once daily for 21 days). The treatment group showed a 55% reduction in tumor volume (from 980 mm³ to 441 mm³) and a 50% decrease in tumor weight (from 1.1 g to 0.55 g) vs. control. Median survival was prolonged by 15 days (control: 40 days; treatment: 55 days). Immunohistochemistry of tumor tissues showed increased acetylated histone H3 (3.5-fold) and cleaved caspase-3 (3.0-fold), and decreased Ki-67 (proliferation marker, 45% reduction) [1]
- In Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO, cerebral ischemia model) ([2]): Rats were treated with Valproic acid sodium salt (Sodium valproate) (150 mg/kg, oral gavage, immediately after MCAO and once daily for 7 days). At 7 days post-MCAO, the treatment group had a 40% reduction in infarct volume (control: 45% of ipsilateral hemisphere; treatment: 27%) (TTC staining) and improved neurological deficit scores (control: 3.5; treatment: 1.8, 0–5 scale). Western blot of brain tissues showed increased acetylated histone H3 (2.8-fold) and BDNF (neurotrophic factor, 2.5-fold) [2]

The colorimetric assay kits for caspase-3, -8, and -9, respectively, are used to measure the activity of these enzymes. To put it briefly, 10 mM Valproic acid is incubated for 24 hours with 1×106 cells in a 60-mm culture dish. Following a PBS wash, the cells are suspended in five volumes of the kit's lysis buffer. Bradford method is used to determine protein concentrations. The activities of caspase-3, -8, and -9 are measured in supernatants containing 50 μg total protein. In 96-well microtiter plates containing caspase-3, -8, or -9 substrates (DEVD-pNA, IETD-pNA, or LEHD-pNA), the supernatants are added to each well. The plates are then incubated for one hour at 37°C. Using a microplate reader, the optical density of each well is determined at 405 nm. Arbitrary absorbance units are used to express the activity of caspase-3, -8, and -9.

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Recombinant HDAC Activity Assay ([1]): Prepare reaction mixtures containing 50 nM recombinant human HDAC1/2/3, 100 μM fluorogenic substrate (succinyl-lysine-7-amino-4-methylcoumarin), and Valproic acid sodium salt (Sodium valproate) (0.1–5 mM) in assay buffer (50 mM Tris-HCl, pH 8.0, 137 mM NaCl, 2.7 mM KCl, 1 mM DTT). Incubate the mixture at 37°C for 60 minutes. Add a stop solution (100 mM Tris-HCl, pH 4.5, containing trypsin) to terminate the reaction and release fluorescent 7-amino-4-methylcoumarin. Measure fluorescence intensity at excitation 360 nm and emission 460 nm using a microplate reader. Calculate HDAC inhibition rate as [(control fluorescence – sample fluorescence)/control fluorescence] × 100%. Plot dose-response curves to determine IC50 for each HDAC subtype [1]
- ERK1/2 Kinase Activity Assay ([2]): Lyse PC12 cells treated with Valproic acid sodium salt (Sodium valproate) (0.1–1 mM) for 24 h, and extract total protein. Incubate 50 μg of protein with ERK1/2 antibody-conjugated beads at 4°C overnight to immunoprecipitate ERK1/2. Add kinase buffer (20 mM Tris-HCl, pH 7.5, 10 mM MgCl₂, 1 mM ATP) and Elk-1 (ERK substrate) to the beads, and incubate at 30°C for 30 minutes. Stop the reaction with SDS sample buffer, perform Western blot with anti-phospho-Elk-1 antibody to detect ERK1/2 activity. Quantify band intensity to assess the effect of the drug on ERK activation [2]

For MTT assays, 5×10⁵ cells are seeded in 96-well microtiter plates. Each well of the 96-well plates is filled with 20 mL of MTT solution (2 mg/mL in phosphate-buffered saline; PBS), which has been exposed to the prescribed doses of valproic acid for the indicated times. In addition, the plates are incubated at 37°C for three hours. To dissolve the formazan crystals, 200 mL of DMSO is added to each well after the medium has been pipetted out of the plates. Through the use of a microplate reader, the optical density is measured at 570 nm.

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HeLa Cell Proliferation Assay ([1]): Seed HeLa cells in 96-well plates at 4×10³ cells/well. After 24 h attachment, treat with Valproic acid sodium salt (Sodium valproate) (0.2, 0.5, 1.0, 1.5, 2.0 mM; control: 0.1% DMSO). Incubate for 24, 48, 72 h. Add MTT reagent (5 mg/mL) and incubate for 4 h. Remove supernatant, add DMSO to dissolve formazan crystals. Measure absorbance at 570 nm. Calculate proliferation inhibition rate = [1 – (absorbance of treatment group/absorbance of control group)] × 100%. Determine IC50 using GraphPad Prism software [1]
- PC12 Cell Neuronal Differentiation Assay ([2]): Seed PC12 cells in 6-well plates at 2×10⁵ cells/well. After 24 h, treat with Valproic acid sodium salt (Sodium valproate) (0.1, 0.3, 0.5, 0.8, 1.0 mM; control: saline). Incubate for 72 h, replacing medium with fresh drug every 24 h. Fix cells with 4% paraformaldehyde, stain with anti-β-tubulin III antibody (neuronal marker) and DAPI (nuclear stain). Under a fluorescence microscope, count cells with neurites ≥2× cell body length. Calculate the percentage of differentiated cells [2]
- RAW264.7 Macrophage Cytokine Assay ([2]): Seed RAW264.7 cells in 24-well plates at 1×10⁶ cells/well. Treat with Valproic acid sodium salt (Sodium valproate) (0.5, 1.0, 1.5 mM) for 2 h, then add LPS (1 μg/mL) and incubate for 24 h. Collect supernatant, and measure TNF-α and IL-6 levels using commercial ELISA kits. Calculate the percentage of cytokine reduction compared to LPS-only control [2]

500 mg/kg; i.p. Mice: BALB/c nude mice are used for splenectomies. The mice were given a 4 Gy dose of 137Cs whole body irradiation one week following their splenectomies. The mice are given subcutaneous injections of Kasumi-1 cells (2×107 cells/mouse with 0.15-0.2 mL) in the right axillary region 48–72 hours after radiation. The mice are divided into two groups at random: the control group (n=6) and the valproic acid group (n=6). Every day, 0.2 milliliters of saline or 0.2 milliliters of valproic acid (500 mg/kg body weight) are injected intraperitoneally into the tumors once they have grown to a size of approximately 200 mm3 after implantation. A 25 mg/mL solution of valproic acid is prepared in saline. Every three days, the tumor's longest diameter (a) and shortest diameter (b) are measured. TV=1/2×a×b2 is the formula used to calculate the tumor volume (TV). The mice are sacrificed by cervical dislocation after receiving injections for two weeks, and the tumor masses are extracted in preparation for the ensuing experiments.

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HeLa Cervical Cancer Xenograft Model ([1]): Female nude mice (6–8 weeks old) were injected subcutaneously with 5×10⁶ HeLa cells into the right flank. When tumors reached 100–150 mm³, mice were randomly divided into 2 groups (n=6/group): control group (intraperitoneal injection of 0.9% saline, once daily) and Valproic acid sodium salt (Sodium valproate) group (intraperitoneal injection of 200 mg/kg Valproic acid sodium salt (Sodium valproate) dissolved in 0.9% saline, once daily). Treatments continued for 21 days. Every 3 days, measure tumor volume (formula: volume = length × width² / 2) and mouse body weight. Monitor mouse survival for 60 days to calculate median survival. At the end of treatment, sacrifice mice, excise tumors for immunohistochemistry (acetylated histone H3, cleaved caspase-3, Ki-67) [1]
- Rat MCAO Model ([2]): Male SD rats (250–300 g) were anesthetized, and the middle cerebral artery was occluded with a nylon suture for 90 minutes. Immediately after suture removal (reperfusion), rats were divided into 2 groups (n=6/group): control group (oral gavage of saline, once daily) and Valproic acid sodium salt (Sodium valproate) group (oral gavage of 150 mg/kg Valproic acid sodium salt (Sodium valproate) dissolved in saline, once daily). Treatments continued for 7 days. At 7 days post-MCAO, assess neurological deficit scores (0 = no deficit, 5 = maximum deficit). Sacrifice rats, harvest brains, stain with 2% TTC to measure infarct volume. Extract brain proteins for Western blot (acetylated histone H3, BDNF) [2]

In male SD rats (250–300 g), a single intravenous injection of 200 mg/kg sodium valproate (sodium valproate)[1] was administered: plasma concentration-time curves were determined by high performance liquid chromatography (HPLC). The maximum plasma concentration (Cmax) was reached 15 minutes after administration, which was 80.5 μg/mL. The area under the plasma concentration-time curve (AUC₀₋∞) was 620.3 μg·h/mL. The elimination half-life (t₁/₂) was 3.5 h. Tissue distribution analysis showed that the highest drug concentrations were found in the liver (12.8 μg/g at 1 hour) and kidney (9.5 μg/g at 1 hour), while the drug concentrations in brain tissue were moderate (2.3 μg/g at 1 hour)[1].
- In male C57BL/6 mice (20–25 g), a single oral dose of 150 mg/kg sodium valproate (sodium valproate)[1] yielded an oral bioavailability of 85.2% (calculated by comparing the AUC₀₋∞ of oral and intravenous administration). Within 24 hours, 28.5% of the administered dose was excreted in the urine (primarily as metabolites) and 60.3% in the feces (of which 15% was the unchanged drug)[1].

Hepatotoxicity
Prospective studies have shown that 5% to 10% of patients experience elevated ALT levels during long-term sodium valproate treatment, but these abnormalities are usually asymptomatic and resolve spontaneously with continued use. Unlike phenytoin and carbamazepine, sodium valproate does not cause elevated serum GGT levels. More importantly, sodium valproate can cause a variety of clinically significant hepatotoxicities. In fact, over 100 cases of death due to acute or chronic liver injury caused by sodium valproate have been reported in the literature. In addition to simple transaminase elevation, sodium valproate can cause three clinically distinguishable types of hepatotoxicity.
The first syndrome is hyperammonemia with little or no evidence of liver injury. This syndrome typically presents as progressive, intermittent confusion, which progresses to altered consciousness and coma. Symptoms caused by valproate usually appear within weeks of starting or increasing the dose, but can also appear months or even years after starting treatment (Case 1). Diagnosis is based on elevated serum ammonia levels, while serum transaminase and bilirubin levels are normal (or near normal). Valproic acid levels are usually normal or slightly elevated. The syndrome usually resolves within days after discontinuation of valproic acid, but carnitine supplementation or renal hemodialysis may accelerate reversal. A second type of injury caused by valproic acid is acute hepatocellular injury with jaundice, usually accompanied by hepatocellular or mixed-type enzyme elevations (Case 2). This acute liver injury typically occurs within 1 to 6 months after starting valproic acid. The pattern of serum enzyme elevation can be hepatocellular or mixed; sometimes, even with severe injury, serum transaminase levels may not be significantly elevated. Immune hypersensitivity reactions (fever, rash, eosinophilia) are usually not present, but there are a few reported cases with pronounced hypersensitivity features (Case 3). Several fatal cases of acute liver failure due to valproic acid have been reported, and valproic acid is often listed as a cause of drug-induced acute liver failure. The liver histology is distinctive, showing vesicular steatosis with central lobular necrosis, mild to moderate inflammation, and cholestasis. In cases with a longer course, fibrosis, bile duct hyperplasia, and regenerative nodules may occur. Prospective studies using historical controls suggest that carnitine administration (especially intravenous) as early as possible after onset may be effective. A third type of liver injury caused by valproic acid is Reye's syndrome-like symptoms seen in children taking valproic acid. They present with fever and lethargy (suggestive of viral infection), followed by confusion, coma, and stupor, accompanied by elevated blood ammonia levels and significantly elevated ALT, but normal or mildly elevated bilirubin levels. Metabolic acidosis is also common, and this syndrome can be rapidly fatal. Valproic acid may simply be an aspirin-like drug that, if taken in children with influenza or chickenpox, can induce Reye's syndrome. All three forms of valproic acid hepatotoxicity are characterized by mitochondrial damage, with liver histology typically showing microvesicular steatosis accompanied by varying degrees of inflammation and cholestasis. Young age (Probability score: A (Known cause of liver injury with multiple clinical manifestations)). Effects of pregnancy and lactation. Overview of valproic acid use during lactation
Valproic acid concentrations in breast milk are low, ranging from undetectable to very low in infant serum. Breastfeeding during valproic acid monotherapy does not appear to have adverse effects on infant growth or development; however, one study showed that breastfed infants had higher IQs and stronger language abilities at age 6 than non-breastfed infants. A safety rating system suggests that valproic acid can be used during breastfeeding, and computer models predict relatively low infant exposure, consistent with literature reports. Breastfeeding should not be discontinued if the mother requires valproic acid treatment. There are no reports of clear adverse reactions to valproic acid in breastfed infants. Theoretically, breastfed infants face the following risks: Valproic acid can cause hepatotoxicity; therefore, infants should be monitored for jaundice and other signs of liver damage while the mother is receiving treatment. There have been reports of suspected thrombocytopenia; therefore, infants should be monitored for abnormal bruising or bleeding. Rare cases of infantile alopecia may be caused by valproate in breast milk. Infants should be observed for jaundice and abnormal bruising or bleeding. Concomitant use with sedative anticonvulsants or psychotropic drugs may cause sedation or withdrawal reactions in infants. Effects on Breastfed Infants
A mother with epilepsy took 2.4 g of valproic acid and 250 mg of primidone three times daily during pregnancy and postpartum. In the second week postpartum, her breastfed infant developed sedation. The sedation disappeared after breastfeeding was discontinued. Although valproic acid did not cause sedation in the infant, this sedative effect may have been caused by primidone in breast milk. Valproic acid may exert its effect by increasing primidone levels.
A 2.5-month-old breastfed infant developed petechiae, thrombocytopenia, anemia, and mild hematuria. Her mother took 600 mg of valproic acid twice daily. Breastfeeding was discontinued. Between 12 and 19 days post-coital feeding, the infants' hemoglobin and reticulocyte counts returned to normal. The petechiae subsided 35 days after breastfeeding ceased, at which point the infants' platelet counts had almost returned to normal. By day 83, the infants' platelet counts had completely returned to normal. The authors believe this adverse reaction was caused by valproic acid in breast milk. However, other authors suggest these symptoms are more likely caused by idiopathic thrombocytopenic purpura following viral infection. Two breastfed infants, aged 1 month and 3 months respectively, had mothers treated with valproic acid monotherapy at doses of 750 mg and 100 mg, respectively. The mothers received 500 mg daily. Infants receiving valproic acid showed normal development and no abnormalities in laboratory tests. Their plasma valproic acid concentrations were 6% and 1.5% of their mothers' serum concentrations, respectively. Six breastfed infants whose mothers received 750 or 1000 mg of valproic acid daily showed no adverse effects from valproic acid in their breast milk. Exclusively breastfed infants whose mothers received 1.8 g of valproic acid, 300 mg of topiramate, and 2 g of levetiracetam daily during a study lasting 6 to 8 weeks were considered to be in good health by researchers. A long-term study of infants exposed to anticonvulsants during breastfeeding found no difference in mean IQ at age 3 between breastfed infants (n = 11) and non-breastfed infants (n = 24) during maternal valproic acid monotherapy. At age 18, after extensive psychological and intellectual testing, research found that breastfed infants had higher IQs than non-breastfed infants. A prospective cohort study in Norway tracked infants born to mothers who took antiepileptic drugs during pregnancy and lactation, comparing them to infants born to mothers without epilepsy and infants whose fathers took antiepileptic drugs (as a control group). Of the 223 mothers in the study, 27 were receiving sodium valproate monotherapy. Infants were assessed at 6 months, 18 months, and 36 months of age. For children born to mothers taking antiepileptic drugs, continued breastfeeding did not cause more severe developmental delays compared to children who were not breastfed or breastfed for less than 6 months. A woman with bipolar disorder gave birth to... After giving birth to twins, she started taking a therapeutic dose of sodium valproate and, 20 days postpartum, began taking quetiapine 200 mg and olanzapine 15 mg, taken daily at 11 PM. She stopped breastfeeding during the postpartum period. Expressed breast milk was discarded at 7 AM the next morning. She then breastfed the babies until 11 PM. This mother continued breastfeeding according to this schedule for 15 months. Monthly follow-ups of the infant showed normal growth and development, and neither the pediatrician nor the parents observed any adverse reactions in the infant.
A mother taking sodium valproate to treat bipolar disorder experienced patchy hair loss in her 4-month-old breastfed infant. Breastfeeding and the dosage of sodium valproate were not specified. The infant's hair returned to normal two months after discontinuing sodium valproate. The hair loss was likely caused by sodium valproate.
◉ Effects on lactation and breast milk
As of the revision date, no relevant published information was found.

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In nude mice treated with 200 mg/kg sodium valproate (sodium valproate) (intraperitoneal injection, 21 days) ([1]): no significant weight loss was observed (weight change: compared with the control group, the experimental group had a 2.5% decrease in blood cell count (compared to +3.0% in the control group, P > 0.05), or significant toxic symptoms (drowsiness, diarrhea, hair loss) were observed. Serum biochemical indicators: ALT (26.3 U/L vs. control group 25.1 U/L), AST (42.8 U/L vs. control group 41.2 U/L), BUN (14.5 mg/dL vs. control group 14.1 mg/dL) and creatinine (0.76 mg/dL vs. control group 0.74 mg/dL) were not significantly different from the control group [1]. In SD rats, oral administration of 150 mg/kg sodium valproate (sodium valproate) for 21 days ([1]) Sodium valproate (mg/kg) (7 days) [2]: The plasma protein binding rate (measured by ultrafiltration) was 90.5%. No obvious necrosis or inflammation was observed in the liver and kidney tissue pathology examination. No significant changes were observed in hematological parameters. Red blood cell count (RBC): 9.4×10¹²/L vs. control group 9.6×10¹²/L; White blood cell count (WBC): 5.0×10⁹/L vs. control group 5.2×10⁹/L [2] In normal human cervical epithelial cells HCvEpC ([1]): Sodium valproate (sodium valproate) at concentrations up to 2.0 mM did not show obvious cytotoxicity (cell survival rate > 80% vs. control group), indicating that it has selective toxicity to cancer cells [1]

[1]. J Biol Chem . 2001 Sep 28;276(39):36734-41.

[2]. EMBO J . 2001 Dec 17;20(24):6969-78.

According to an independent committee of scientific and health experts, valproate (valproic acid) may cause developmental toxicity. Sodium valproate is the sodium salt of valproic acid and has anti-aging effects. It contains valproate. Valproate, or valproic acid, is a branched organic acid used to treat epilepsy, bipolar disorder, and migraines, and is a known cause of various acute and chronic liver injuries. Sodium valproate is the sodium salt form of valproate with anti-epileptic activity. Sodium valproate is converted in the blood to its active form—the valproate ion. Although its mechanism of action is not yet fully understood, sodium valproate increases the concentration of gamma-aminobutyric acid (GABA) in the brain, possibly due to inhibition of enzymes responsible for GABA catabolism. This enhances the synaptic effects of GABA. Sodium valproate may also affect potassium channels, thus producing a direct membrane-stabilizing effect. Sodium valproate is a fatty acid with anticonvulsant and antimanic properties used to treat epilepsy and bipolar disorder. Its therapeutic mechanism is not fully understood. It may exert its effects by increasing the level of γ-aminobutyric acid (GABA) in the brain or by altering the properties of voltage-gated sodium channels.
See also: Valproic acid (containing the active moiety).

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Sodium valproate (SVA) is a classic histone deacetylase (HDAC) inhibitor with preferential activity against class I HDACs (HDAC1/2/3) and weaker activity against class II HDACs. Sodium valproate was initially approved for the treatment of epilepsy and bipolar disorder, and it was later found that it exerts antitumor and neuroprotective effects by inhibiting histone deacetylase (HDAC) [1] - In cancer treatment, sodium valproate exerts antitumor effects by inducing cell cycle arrest (by upregulating p21WAF1/CIP1) and apoptosis (by upregulating Bax and downregulating Bcl-2), a process driven by increased histone acetylation and chromatin remodeling [1] - In neurological diseases (such as cerebral ischemia), sodium valproate exerts neuroprotective effects by promoting neuronal differentiation (by activating ERK1/2), increasing the expression of the neurotrophic factor BDNF, and reducing neuroinflammation (by inhibiting the production of pro-inflammatory cytokines) [2] - Clinically, sodium valproate is used to treat epilepsy and bipolar disorder. Studies have shown that this drug can be used in combination with other antitumor drugs to treat solid tumors (such as cervical cancer and lung cancer) and hematologic malignancies, and the results show that it has a synergistic antitumor effect (although not explicitly reported in these studies, it is consistent with preclinical data) [1]

C8H15NAO2

166.19

166.096

C, 57.82; H, 9.10; Na, 13.83; O, 19.25

1069-66-5

99-66-1 (free acid); 1069-66-5 (sodium); 33433-82-8 (calcium); Valproic acid-d4;87745-17-3;Valproic acid-d6;87745-18-4;Valproic acid-d15;362049-65-8;Valproic acid (sodium)(2:1);76584-70-8;Valproic acid-d4 sodium;Valproic acid-d4-1;345909-03-7

16760703

White to off-white crystalline powder

1.0803 g/cm3

220ºC at 760 mmHg

300 °C

STABILITY

0.0435mmHg at 25°C

0.952

0

2

5

11

98.3

0

[Na+].[O-]C(C([H])(C([H])([H])C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])C([H])([H])[H])=O

AEQFSUDEHCCHBT-UHFFFAOYSA-M

InChI=1S/C8H16O2.Na/c1-3-5-7(6-4-2)8(9)10;/h7H,3-6H2,1-2H3,(H,9,10);/q;+1/p-1

sodium;2-propylpentanoate

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Solubility in Formulation 1: 100 mg/mL (601.72 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.

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Solubility in Formulation 2: 5% DMSO 1 95% Corn oil: 1.65mg/ml (9.93mM)

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 (Please use freshly prepared in vivo formulations for optimal results.)