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Valproic Acid

drug
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Also known as Acide valproiqueAcido valproicoConvulexDepakeneDepakoteNSC-93819StavzorValproateValproic acid extended releasevalporic acidSID17389523SID90341449SID26752921SID399407ACIDE_VALPROIQUESID174007029SID144209161SID170465446SID144210920

Summary

Valproic Acid (CHEMBL109) is an approved small-molecule antimanic drug (ATC N03AG01) targeting HDAC1; indicated across 66 conditions including epilepsy and complex partial epilepsy; with CIViC clinical evidence for 2 variant-indication associations (e.g. NPM1 EXON 11 MUTATION in acute myeloid leukemia).

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: N03AG01
  • Targets: 1 (HDAC1)
  • Indications: 66 conditions
  • Clinical trials: 165
  • Precision-oncology evidence (CIViC): 2 variant–indication associations
  • Chemistry: 144.21 Da · C8H16O2

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL109
NameValproic Acid
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID3121
ChEBICHEBI:39867
ATCN03AG01
Molecular formulaC8H16O2
Molecular weight144.21
InChIKeyNIJJYAXOARWZEE-UHFFFAOYSA-N

SMILES: CCCC(CCC)C(=O)O

IUPAC name: 2-propylpentanoic acid

ChEBI definition: A branched-chain saturated fatty acid that comprises of a propyl substituent on a pentanoic acid stem.

Pharmacological roles (ChEBI): antimanic drug, anticonvulsant, GABA agent, EC 3.5.1.98 (histone deacetylase) inhibitor, teratogenic agent, psychotropic drug, neuroprotective agent.

Also known as: Acide valproique, Acido valproico, Convulex, Depakene, Depakote, NSC-93819, Stavzor, Valproate, Valproic acid, Valproic acid extended release, valproic acid, valporic acid

Parent form; salt/anhydrous children: CHEMBL433, CHEMBL2105613, CHEMBL2315212

Patent coverage: 17,732 distinct patent families (65,937 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

GeneTargetActionpAffinityCancer dependencyUniProt
HDAC1histone deacetylase 1Inhibition3.44.5%Q13547

Broader ChEMBL bioactivity targets: 16 (assay-derived). Sample: Tyrosyl-DNA phosphodiesterase 1, Histone deacetylase 2, Muscarinic acetylcholine receptor M1, 5-hydroxytryptamine receptor 2A, Aldo-keto reductase family 1 member A1, 5-hydroxytryptamine receptor 2C, Alpha-1A adrenergic receptor, Histamine H1 receptor, D(3) dopamine receptor, Sodium-dependent dopamine transporter.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 25 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
HRH17AC50100nMCHEMBL_ACT_25212771
HTR2A6.78AC50165.8nMCHEMBL_ACT_25173700
CHRM16.07AC50850nMCHEMBL_ACT_25135716
ADRA1A5.96AC501094nMCHEMBL_ACT_25138078
CHRM35.89AC501300nMCHEMBL_ACT_25136936
TDP15.6Potency2512nMCHEMBL_ACT_3939718
DRD35.33AC504700nMCHEMBL_ACT_25193783
SLC6A35.3AC504970nMCHEMBL_ACT_25124204

Target pathways

Aggregated over 1 target gene(s): HDAC1.

Top Reactome pathways

42 total, by targets touching each:

PathwayTargetsGenes
Transcription of E2F targets under negative control by DREAM complex1HDAC1
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC11HDAC1
G0 and Early G11HDAC1
p75NTR negatively regulates cell cycle via SC11HDAC1
Formation of the beta-catenin:TCF transactivating complex1HDAC1
NOTCH1 Intracellular Domain Regulates Transcription1HDAC1
Downregulation of SMAD2/3:SMAD4 transcriptional activity1HDAC1
SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription1HDAC1
Constitutive Signaling by NOTCH1 PEST Domain Mutants1HDAC1
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants1HDAC1
HDACs deacetylate histones1HDAC1
Notch-HLH transcription pathway1HDAC1
Deactivation of the beta-catenin transactivating complex1HDAC1
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression1HDAC1
NoRC negatively regulates rRNA expression1HDAC1
SUMOylation of chromatin organization proteins1HDAC1
Repression of WNT target genes1HDAC1
Regulation of TP53 Activity through Acetylation1HDAC1
G1/S-Specific Transcription1HDAC1
RNA Polymerase I Transcription Initiation1HDAC1
RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function1HDAC1
Regulation of PTEN gene transcription1HDAC1
Estrogen-dependent gene expression1HDAC1
Loss of MECP2 binding ability to 5mC-DNA1HDAC1
Regulation of MECP2 expression and activity1HDAC1
MECP2 regulates neuronal receptors and channels1HDAC1
MECP2 regulates transcription of neuronal ligands1HDAC1
FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes1HDAC1
Potential therapeutics for SARS1HDAC1
STAT3 nuclear events downstream of ALK signaling1HDAC1

Dominant GO biological processes

GO termTargets
negative regulation of transcription by RNA polymerase II1
chromatin organization1
chromatin remodeling1
DNA methylation-dependent constitutive heterochromatin formation1
regulation of transcription by RNA polymerase II1
endoderm development1
positive regulation of cell population proliferation1
epidermal cell differentiation1
positive regulation of gene expression1
negative regulation of gene expression1
hippocampus development1
neuron differentiation1
negative regulation of cell migration1
negative regulation of transforming growth factor beta receptor signaling pathway1
heterochromatin formation1

Indications & clinical

Indications

66 indications (8 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

IndicationTrial phaseMONDOEFO
epilepsy4MONDO:0005027EFO:0000474
complex partial epilepsy4MONDO:0006710EFO:1000877
visual epilepsy4MONDO:0001386HP:0001250
inborn mitochondrial metabolism disorder4MONDO:0004069MONDO:0044970
bipolar disorder4MONDO:0004985MONDO:0004985
anxiety3MONDO:0011918EFO:0005230
tropical spastic paraparesis3MONDO:0008039EFO:0007527
dementia3MONDO:0001627HP:0000726
depressive disorder3MONDO:0002050MONDO:0002050
Alzheimer disease3MONDO:0004975MONDO:0004975
migraine disorder3MONDO:0005277MONDO:0005277
autism3MONDO:0005260EFO:0003758
alcohol abuse3MONDO:0002046MONDO:0007079
spinal muscular atrophy3MONDO:0001516MONDO:0019079
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
HIV infectious disease2MONDO:0005109EFO:0000764
head and neck squamous cell carcinoma2MONDO:0010150EFO:0000181
thyroid tumor2MONDO:0015074EFO:0003841
neuralgia2MONDO:0021667EFO:0005762
androgenetic alopecia2MONDO:0005339EFO:0004191
B-cell chronic lymphocytic leukemia2MONDO:0004948EFO:0000095
myelodysplastic syndrome2MONDO:0018881EFO:0000198
acute myeloid leukemia2MONDO:0018874EFO:0000222
chronic myeloid leukemia2MONDO:0011996EFO:0000339
glioblastoma2MONDO:0018177EFO:0000519
leukemia2MONDO:0005059EFO:0000565
lymphoma2MONDO:0005062EFO:0000574
small cell lung carcinoma2MONDO:0008433EFO:0000702
head and neck cancer2MONDO:0005627EFO:0006859
breast neoplasm2MONDO:0021100MONDO:0007254
glioma2MONDO:0021042MONDO:0100342
brain neoplasm2MONDO:0021211EFO:0003833
progressive supranuclear palsy2MONDO:0019037MONDO:0019037
retinitis pigmentosa2MONDO:0019200MONDO:0019200
ependymoma2MONDO:0016698MONDO:0003478
sarcoma1MONDO:0005089EFO:0000691
melanoma1MONDO:0005105EFO:0000756
non-small cell lung carcinoma1MONDO:0005233EFO:0003060
injury1MONDO:0021178EFO:0000546
Burkitt lymphoma1MONDO:0007243EFO:0000309
diffuse large B-cell lymphoma1MONDO:0018905EFO:0000403
neoplasm1MONDO:0005070EFO:0000616
ovarian carcinoma1MONDO:0005140EFO:0001075
anaplastic astrocytoma1MONDO:0016684EFO:0002499
medulloblastoma1MONDO:0007959EFO:0002939
mantle cell lymphoma1MONDO:0018876EFO:1001469
soft tissue sarcoma1MONDO:0018078EFO:1001968
central nervous system neoplasm1MONDO:0006130EFO:1000158
lung neoplasm1MONDO:0021117MONDO:0008903
focal epilepsy1MONDO:0005384EFO:0004263
paraganglioma1MONDO:0000448EFO:1000453
colorectal neoplasm1MONDO:0005335MONDO:0005575
nasopharyngeal carcinoma1MONDO:0015459MONDO:0015459
brain injury1MONDO:0043510MONDO:0043510

12 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 165.

Phase distribution

PhaseTrials
PHASE140
PHASE235
PHASE425
PHASE322
Not specified20
PHASE1/PHASE215
EARLY_PHASE15
PHASE2/PHASE33

Top trials by phase / activity

NCTPhaseStatusTitle
NCT03048084PHASE4RECRUITINGSeizure Treatment in Glioma
NCT06485726PHASE4RECRUITINGValproate Versus Propranolol in Migraine
NCT00194025PHASE4COMPLETEDValproate in Late Life Schizophrenia
NCT00211250PHASE4COMPLETEDComparing Compliance, Tolerability, Efficacy and Adverse Events in Bipolar Tients From Valproic Acid to Depakote ER
NCT00298857PHASE4TERMINATEDA Pharmacokinetic Study to Compare the Dosing of Valproic Acid in Subjects With Different Body Weights
NCT00367874PHASE4COMPLETEDTreatment of Polydrug-Using Opiate Dependents During Withdrawal
NCT00385411PHASE4COMPLETEDStudy of Valproate in Young Patients Suffering From Epilepsy
NCT00484471PHASE4COMPLETEDABLE: Abilify in Bipolar Disorder for Long-term Effectiveness
NCT00545675PHASE4COMPLETEDAbilify in Bipolar Disorder for 24 Weeks Treatment Effectiveness
NCT00609245PHASE4COMPLETEDEffect of Valproic Acid Concentration on Photic Response
NCT00794625PHASE4UNKNOWNEffectiveness of Combined Medication Treatment for Aggression in Children With Attention Deficit With Hyperactivity Disorder (The SPICY Study)
NCT00807989PHASE4COMPLETEDThe Efficacy and Safety of Low Dose Combination of LTG and VPA Compared to CBZ Monotherapy
NCT00854581PHASE4TERMINATEDZidovudine, Interferon Alfa-2b, PEG-Interferon Alfa-2b in Patients With HTLV-I Associated Adult T-Cell Leukemia/Lymphoma
NCT01075126PHASE4WITHDRAWNSafety Study of Depakote Versus Lithium in African Americans With Bipolar Disorder
NCT01115959PHASE4COMPLETEDSeizures Post Intracerebral Hemorrhage
NCT01267864PHASE4COMPLETEDValproate Versus Ketorolac Versus Metoclopramide
NCT01893229PHASE4UNKNOWNComparative Efficacy and Acceptability of Antimanic Drugs in Acute Mania
NCT02343575PHASE4TERMINATEDValproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU
NCT02870283PHASE4COMPLETEDCost- Effectiveness and Quality of Life Assessment in Mood Disorder
NCT03235531PHASE4UNKNOWNAssessment of Valproate on Ethanol Withdrawal
NCT03914534PHASE4COMPLETEDBioequivalence Study of Sodium Divalproate Tablets 500 mg
NCT03940326PHASE4COMPLETEDLevetiracetam Versus Valproate in Idiopathic Generalized Tonic-clonic Seizures
NCT04513314PHASE4WITHDRAWNValproate Alone or in Combination With Quetiapine for Severe COVID-19 Pneumonia With Agitated Delirium
NCT05697614PHASE4UNKNOWNThe Benefit and Safety of Older Generation Anti-Epileptic Drugs (AEDs) in Drug-Resistant Epilepsy Children
NCT06089356PHASE4UNKNOWNZolmitriptane as Prophylaxis for Chilhood Migraine
NCT02265770PHASE2/PHASE3RECRUITINGAn International Clinical Program for the Diagnosis and Treatment of Children With Ependymoma
NCT05431595PHASE2/PHASE3RECRUITINGManaging Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy
NCT05603104PHASE3RECRUITINGIntensified Pharmacological Treatment for Schizophrenia, Major Depressive Disorder and Bipolar Depression After a First-time Treatment Failure
NCT05973786PHASE3RECRUITINGThe Effect of a Six Week Intensified Pharmacological Treatment for Bipolar Depression Compared to Treatment as Usual in Subjects Who Had a First-time Treatment Failure on Their First-line Treatment.
NCT06929273PHASE3RECRUITINGA Study to Assess the Long-term Safety of KarXT for the Treatment of Manic Episodes in Bipolar-I Disorder (BALSAM-3)
NCT00057681PHASE3COMPLETEDStudy of Outcome and Safety of Lithium, Divalproex and Risperidone for Mania in Children and Adolescents
NCT00065884PHASE3UNKNOWNValproate Response in Aggressive Autistic Adolescents
NCT00071721PHASE3COMPLETEDValproate in Dementia (VALID)
NCT00088452PHASE3COMPLETEDChildhood Absence Epilepsy Rx PK-PD-Pharmacogenetics Study
NCT00221403PHASE3COMPLETEDPlacebo Controlled Trial of Valproate and Risperidone in Young Children With Bipolar Disorders
NCT00266630PHASE3COMPLETEDEfficacy and Safety of Olanzapine in the Extended Treatment for Manic or Mixed Episode of Bipolar I Disorder
NCT00665366PHASE3COMPLETEDStudy to Evaluate the Efficacy and Safety of Aripiprazole Administered With Lithium or Valproate Over 12 Weeks in the Treatment of Mania in Bipolar I Disorder
NCT00681980PHASE3COMPLETEDUse Of Valproid Acid To Treat Tropical Spastic Paraparesis/HTLV-1-Associated Myelopathy (TSP/HAM)
NCT01188265PHASE3COMPLETEDAdd-on Dextromethorphan in Bipolar Disorders
NCT01342549PHASE3COMPLETEDTreatment Strategy for Alcohol Use Disorders in Veterans With TBI

Clinical evidence (CIViC)

Variant × indication × effect (2 predictive associations from 2 curated evidence items):

VariantIndicationEffectTherapyLevelCIViC
NPM1 EXON 11 MUTATIONAcute Myeloid LeukemiaSensitivity/ResponseValproic AcidCIViC BEID148
BAP1 MutationUveal MelanomaSensitivity/ResponseTrichostatin A + Vorinostat + Panobinostat + Valproic AcidCIViC DEID1234

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 24 clinical and 168 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

42 molecules share ≥1 primary target. Top 42 by shared-target count:

MoleculeSourceStatusShared targets
ATORVASTATINChEMBLPhase 4 (approved)HDAC1
BELINOSTATChEMBLPhase 4 (approved)HDAC1
BENDAMUSTINEChEMBLPhase 4 (approved)HDAC1
BORTEZOMIBChEMBLPhase 4 (approved)HDAC1
CELECOXIBChEMBLPhase 4 (approved)HDAC1
DAUNORUBICINChEMBLPhase 4 (approved)HDAC1
EXIFONEChEMBLPhase 4 (approved)HDAC1
GIVINOSTATChEMBLPhase 4 (approved)HDAC1
LOVASTATINChEMBLPhase 4 (approved)HDAC1
MOMELOTINIBChEMBLPhase 4 (approved)HDAC1
PANOBINOSTATChEMBLPhase 4 (approved)HDAC1
PHENYLBUTANOIC ACIDChEMBLPhase 4 (approved)HDAC1
ROMIDEPSINChEMBLPhase 4 (approved)HDAC1
SODIUM PHENYLBUTYRATEChEMBLPhase 4 (approved)HDAC1
VORINOSTATChEMBLPhase 4 (approved)HDAC1
ABEXINOSTATChEMBLPhase 3HDAC1
CAFFEIC ACIDChEMBLPhase 3HDAC1
CURCUMINChEMBLPhase 3HDAC1
ENTINOSTATChEMBLPhase 3HDAC1
PRACINOSTATChEMBLPhase 3HDAC1
TACEDINALINEChEMBLPhase 3HDAC1
TUCIDINOSTATChEMBLPhase 3HDAC1
AR-42ChEMBLPhase 2HDAC1
BAICALEINChEMBLPhase 2HDAC1
BUTYRIC ACIDChEMBLPhase 2HDAC1
CHLOROGENIC ACIDChEMBLPhase 2HDAC1
CITARINOSTATChEMBLPhase 2HDAC1
DACINOSTATChEMBLPhase 2HDAC1
DOMATINOSTATChEMBLPhase 2HDAC1
FIMEPINOSTATChEMBLPhase 2HDAC1
MOCETINOSTATChEMBLPhase 2HDAC1
MOLIBRESIBChEMBLPhase 2HDAC1
NANATINOSTATChEMBLPhase 2HDAC1
NICOXAMATChEMBLPhase 2HDAC1
QUISINOSTATChEMBLPhase 2HDAC1
RESMINOSTATChEMBLPhase 2HDAC1
RICOLINOSTATChEMBLPhase 2HDAC1
SODIUM BUTYRATEChEMBLPhase 2HDAC1
TINOSTAMUSTINEChEMBLPhase 2HDAC1
CrizotinibPubChemApprovedHDAC1
IdelalisibPubChemApprovedHDAC1
PazopanibPubChemApprovedHDAC1

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 30

This page pulls from 30 datasets indexed by BioBTree:

chebichembl_activitychembl_moleculechembl_targetcivic_evidenceclingen_dosageclinical_trialsdepmapefoensemblentrezgogoparentgtopdbgtopdb_interactiongtopdb_ligandhgncmeshmondomsigdbpatent_compoundpharmgkbpharmgkb_guidelinepubchempubchem_activityreactomereactomeparentrefseqtranscriptuniprot