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    Valproic acid sodium salt (Sodium valproate)
    Valproic acid sodium salt (Sodium valproate)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V0291
    CAS #: 1069-66-5Purity ≥98%

    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 an inhibitor of histone deacetylase (HDAC) with IC50 values in the range of 0.5 and 2 mM.

    References: J Biol Chem. 2001 Sep 28;276(39):36734-41; EMBO J. 2001 Dec 17;20(24):6969-78.

    Related CAS #: 99-66-1 (free acid); 1069-66-5 (sodium); 33433-82-8 (calcium) 

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    Molecular Weight (MW)166.19
    FormulaC8H15NaO2
    CAS No.1069-66-5
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    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)

    Chemical Name: sodium 2-propylpentanoate

    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

    SMILES Code: CCCC(CCC)C([O-])=O.[Na+]

    SynonymsValproic acid sodium salt; Valproic Acid, Convulex, Depakote, Epilim, Stavzor, Vilapro, VPA, Sodium valproate


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    In Vitro

    In vitro activity: Valproic acid acts through a distinct pathway that involves direct inhibition of histone deacetylase (IC(50) for HDAC1 = 0.4 mM). Valproic acid mimics the histone deacetylase inhibitor trichostatin A, causing hyperacetylation of histones in cultured cells. Valproic acid, like trichostatin A, also activates transcription from diverse exogenous and endogenous promoters. Valproic acid and trichostatin A have remarkably similar teratogenic effects in vertebrate embryos, while non-teratogenic analogues of valproic acid do not inhibit histone deacetylase and do not activate transcription. Valproic acid induces proliferation of peroxisomes in the rodent liver. Valproic acid at a concentration of 1 mM induces relief of this repression by Gal4 fusions of N‐CoR, TR or PPARδ in a cell line expressing the ligand‐binding domain of PPARδ fused to the DNA‐binding domain of the glucocorticoid receptor (GR) together with a GR‐controlled reporter gene. Valproic acid induces accumulation of hyperacetylated histone and inhibits HDAC activity. Valproic acid induces a specific type of differentiation characterized by reduced proliferation, morphological alterations, marker gene expression and particularly the accumulation of the AP-2 transcription factor as a potential marker of neuronal or neural crest cell-like differentiation in F9 teratocarcinoma cells. Valproic acid impairs cell proliferation or survival as indicated by decreased incorporation of [3H]thymidine in F9 and P19 teratocarcinoma cells.


    Kinase Assay: 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.


    Cell Assay: 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.

    In VivoValproic acid (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 group is 57.25% at the end of the experiment. Valproic acid (350 mg/kg, i.p.) demonstrates more social investigation and play fighting than control animals
    Animal modelMice: 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.
    Formulation & Dosage500 mg/kg; i.p.
    References

    J Biol Chem. 2001 Sep 28;276(39):36734-41; EMBO J. 2001 Dec 17;20(24):6969-78; Zhang ZH, et al. Valproic acid inhibits tumor angiogenesis in mice transplanted with Kasumi 1 leukemia cells. Mol Med Rep. 2013 Nov 28.


    These protocols are for reference only. InvivoChem does not independently validate these methods.

     
    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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