Valproic acid sodium salt (Sodium valproate)

Alias: Valproic acid sodium salt; Valproic Acid; Convulex; Depakote; Epilim; Stavzor; Vilapro; VPA; Sodium valproate
Cat No.:V0291 Purity: ≥98%
Valproate (VPA, NSC-93819, valproic acid, sodium valproate, and divalproex sodium) is an approved medication mainly used for the treatment of epilepsy and bipolar disorder, also used to prevent migraine headaches.
Valproic acid sodium salt (Sodium valproate) Chemical Structure CAS No.: 1069-66-5
Product category: HDAC
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description

Valproate (VPA, NSC-93819, valproic acid, sodium valproate, and divalproex sodium) is an approved medication mainly used for the treatment of epilepsy and bipolar disorder, also used to prevent migraine headaches. It is a histone deacetylase (HDAC) inhibitor with an IC50 between 0.5 and 2 mM.

Biological Activity I Assay Protocols (From Reference)
Targets
HDAC1 ( IC50 = 400 μM ); HDAC1 ( IC50 = 0.5-2 mM ); HDAC2; Autophagy; Mitophagy
ln Vitro

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]

ln Vivo
Valproic acid inhibits the growth of the primary tumors in the breast cancer model of MT-450 rats. [2]/td>
Enzyme Assay
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.
Cell Assay
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.
Animal Protocol
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.
References

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

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

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C8H15NAO2
Molecular Weight
166.19
Exact Mass
166.1
Elemental Analysis
C, 57.82; H, 9.10; Na, 13.83; O, 19.25
CAS #
1069-66-5
Related CAS #
99-66-1 (free acid); 1069-66-5 (sodium); 33433-82-8 (calcium)
Appearance
White to off-white crystalline powder
SMILES
CCCC(CCC)C(=O)[O-].[Na+]
InChi Key
AEQFSUDEHCCHBT-UHFFFAOYSA-M
InChi Code
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
Chemical Name
sodium;2-propylpentanoate
Synonyms
Valproic acid sodium salt; Valproic Acid; Convulex; Depakote; Epilim; Stavzor; Vilapro; VPA; Sodium valproate
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: ~33 mg/mL (~198.6 mM)
Water: ~33 mg/mL (~198.6 mM)
Ethanol: ~33 mg/mL (~198.6 mM)
Solubility (In Vivo)
5% DMSO 1 95% Corn oil: 1.65mg/ml (9.93mM) (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 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

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
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Calculation results

Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
             (2) Be sure to add the solvent(s) in order.

Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT00431522 Completed Drug: Valproic acid, sodium
salt
Bipolar Disorder Sanofi December 2004 Phase 4
NCT05017454 Completed Drug: the optimized sodium
valproate-loaded nanospanlastic
dispersion
Drug: mometasone furoate
lotion
Alopecia Areata Kasr El Aini Hospital May 1, 2021 Early Phase 1
NCT04531592 Withdrawn Drug: Valproic acid
Drug: Isotonic saline solution
Acute Kidney Injury
Ischemia Reperfusion Injury
Westat January 2022 Phase 2
NCT04531579 Withdrawn Drug: Isotonic saline solution Ischemia Reperfusion Injury
Acute Kidney Injury
Westat January 2022 Phase 2
Biological Data
  • Valproic acid sodium salt (Sodium valproate)
    VPA relieves HDAC-mediated transcriptional repression.EMBO J.2001 Dec 17;20(24):6969-78.
  • Valproic acid sodium salt (Sodium valproate)
    VPA induces accumulation of hyperacetylated histone and inhibits HDAC activity.EMBO J.2001 Dec 17;20(24):6969-78.
  • Valproic acid sodium salt (Sodium valproate)
    HDAC inhibition by compounds related to VPA.EMBO J.2001 Dec 17;20(24):6969-
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