Valproic acid

For research use only. Not for use in humans.

Catalog No.S3944 Synonyms: 2-Propylvaleric Acid, Sodium valproate

8 publications

Valproic acid Chemical Structure

Molecular Weight(MW): 144.21

Valproic acid is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. It is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers.

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Description Valproic acid is a fatty acid with anticonvulsant properties used in the treatment of epilepsy. It is also a histone deacetylase inhibitor and is under investigation for treatment of HIV and various cancers.
HDAC1 [1]
(Cell-free assay)
0.4 mM
In vitro

Valproic acid (VPA), like lithium, activates Wnt-dependent gene expression, but unlike lithium, VPA does not inhibit GSK-3β in vivo. VPA can inhibit GSK-3β-mediated phosphorylation of a CREB peptide in vitro. VPA may activate Wnt-dependent gene expression through inhibition of HDAC, which in turn leads to both increased expression of β-catenin and de-repression of Tcf/Lef (as well as activation of other HDAC-regulated genes). In vitro, VPA can stimulate glutamic acid decarboxylase, which is involved in GABA biosynthesis, and inhibit GABA transaminase, succinic semialdehyde dehydrogenase, and α-ketoglutarate dehydrogenase, enzymes involved in GABA degradation[1]. Valproic acid relieves HDAC-dependent transcriptional repression and causes hyperacetylation of histones in cultured cells and in vivo. VPA induces differentiation and/or apoptosis of carcinoma cells, PML-RAR-transformed hematopoietic progenitor cells and leukemic blasts from AML patients[2]. In addition to selectively inhibiting the catalytic activity of class I HDACs, VPA also induces proteasomal degradation of HDAC2[3].

Methods Test Index PMID
Western blot

PubMed: 20025549     

Changes in histone acetylation after valproic acid (VPA) exposure. LS174T and HCT116 cells were exposed to varying concentrations of VPA for 16 hours. Cellular protein extracts were prepared, as described in Materials and Methods, and analyzed by immunoblot assay with antibody against acetylated histone H4 (acetyl-H4). β-actin was included as a control to show equivalent protein loading.


PubMed: 30387821     

Chidamide and VPA promoted an increase in the levels of histone H3 acetylation in human MM cells (RPMI-8226 and U266). 

p-IKKα/β / IKKα/β / NF-κB p65 / IκBα; 

PubMed: 30387821     

(C) Effects of VPA (1 mM) on the expression levels of NF-κB pathway-associated proteins in U266 cells. (D) Effects of VPA (0.5 mM) on the expression levels of NF-κB pathway-associated proteins in RPMI8226 cells. IκBα, inhibitor of NF-κB; IKK, IκB kinase; NF-κB, nuclear factor-κB; p, phosphorylated; VPA, valproic acid.

20025549 30387821
Growth inhibition assay
Cell viability; 

PubMed: 28101176     

Inhibitory effect of various doses of VPA on CAL27 cell proliferation. CAL27 cells were treated with 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mm/l VPA for 24, 48, 72, 96 and 120 h, respectively, in vitro. Cell viability was determined using MTT assay and analyzed as the percentage of the absorbance value compared with control. *P<0.05 vs. 0.0 mmol/l; #P<0.05 vs. 0 h. Error bars represent the standard error of the mean. VPA, valproic acid.

In vivo Valproic acid (VPA) increases the level of the inhibitory neurotransmitter γ-aminobutyric acid (GABA), with acute administration causing a 15-45% increase in GABA in the brains of rodents[1]. VPA also inhibits tumor growth and metastasis in animal experiments. It is a well-tolerated drug even during long-term treatment[2].


Cell Research:


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  • Cell lines: Neuro2A cells
  • Concentrations: 0.5-5 mM
  • Incubation Time: 24 h
  • Method:

    Neuro2A cells are treated with VPA (0.5-5 mM) or with TSA (300 nm) for 24 h and then histones are isolated. Histone acetylation is assessed by immunoblotting with an antibody specific to acetylated histone H4.

    (Only for Reference)
Animal Research:


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  • Animal Models: Rats
  • Formulation: isotonic saline
  • Dosages: 1.25 mM/kg
  • Administration: i.p.
    (Only for Reference)

Solubility (25°C)

Chemical Information

Molecular Weight 144.21


CAS No. 99-66-1
Storage powder
in solvent
Synonyms 2-Propylvaleric Acid, Sodium valproate
Smiles CCCC(CCC)C(O)=O

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Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03962829 Recruiting Drug: mCPP|Drug: Placebo oral tablet Eating Behavior|Obesity University of Birmingham|University Hospital Birmingham February 1 2019 Not Applicable
NCT03681158 Completed Drug: sodium valproate Epilepsy Sanofi October 5 2018 Phase 1
NCT03525730 Recruiting Drug: Valproic Acid|Drug: Pyrimethamine HIV-1-infection Erasmus Medical Center April 18 2018 Phase 1|Phase 2
NCT03357757 Recruiting Drug: Valproic Acid|Biological: Avelumab Cancer That is Associated With a Chronic Viral Infection|p16 Positive SCCHN|Squamous Cell Carcinoma of the Cervix|p16 Positive Squamous Cell Carcinoma of the Vagina or Vulva|p16 Positive Squamous Cell Carcinoma of the Penis|p16 Positive Squamous Cell Carcinoma of the Anus or Anal Canal|EBER Positive NPC|EBER Positive Hodgkins and Non-hodgkins Lymphona AHS Cancer Control Alberta|EMD Serono February 7 2018 Phase 2
NCT02607891 Completed Drug: GWP42003-P|Drug: Placebo Epilepsy GW Research Ltd November 9 2016 Phase 2
NCT02896270 Recruiting Drug: Valproic Acid Idiopathic Nephrotic Syndrome|Focal Segmental Glomerulosclerosis|Minimal Change Disease Universitair Ziekenhuis Brussel October 2016 Phase 2|Phase 3

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID