DRUG

valproic acid

Epilepsy, bipolar disorder, migraine prophylaxis

135 hypotheses across 10 therapeutic domains

CROSS-DOMAIN PATTERN

Same drug, multiple disease domains

valproic acid appears in hypotheses across 10 disease domains: ALS, Alzheimer, Depression, Epilepsy, Glioblastoma, Inflammatory bowel disease, Multiple sclerosis, Pancreatic cancer, Rheumatoid arthritis, Type 2 diabetes. Shared mediators that recur across at least two of those domains: VEGF, BDNF, galectin-3, NRF2, COX-2, DNA methylation.

Aggregated from the catalog. Biological interpretation of any multi-indication mechanism would require independent validation — this is a structural observation only.

ALL HYPOTHESES

Repurposing candidates for valproic acid

ALS 18

Mediator Outcome Score Tier Lit. status Trial
histone deacetylase amyotrophic lateral sclerosis 0.345 High reproduces known completed
mTOR signaling VAP(P58S) aggregation 0.269 Mid novel signal none
NRF2 neurodegenerative processes 0.269 Mid novel signal active
BDNF disease progression 0.208 Mid reproduces known active
Progranulin dopaminergic neuron degeneration 0.208 Mid novel signal none
galectin-3 neurological distemper 0.208 Mid novel signal none
galectin-3 limb onset ALS 0.208 Mid novel signal none
galectin-3 female gender in ALS 0.208 Mid novel signal none
galectin-3 disease duration >12 months 0.208 Mid novel signal none
Kir4.1 peak strength 0.208 Mid novel signal none
galectin-3 disease duration 0.208 Mid reproduces known active
β-catenin motor neuron degeneration 0.208 Mid novel signal none
Progranulin loss of large axon fibers 0.208 Mid novel signal none
Progranulin survival 0.208 Mid reproduces known completed
Progranulin axonal degeneration 0.208 Mid partial evidence none
NF-κB signaling pathway ALS pathogenesis 0.208 Mid novel signal none
VEGF susceptibility to neurodegeneration 0.208 Mid novel signal none
BDNF disease duration 0.208 Mid reproduces known active

Alzheimer 10

Mediator Outcome Score Tier Lit. status Trial
HDAC2 cholinergic nbM neuronal dysfunction 0.312 High novel signal none
TREM2 Alzheimer's disease 0.248 Mid reproduces known completed
Progranulin neurofibrillary tangle development 0.208 Mid novel signal none
BDNF neuritic plaque pathology 0.208 Mid novel signal completed
VEGF vascular dementia 0.208 Mid partial evidence none
VEGF amyloid-β burden 0.208 Mid novel signal none
COX-2 Alzheimer's disease 0.208 Mid reproduces known completed
DNA methylation behavioral performance 0.208 Mid partial evidence none
BDNF neurodegenerative changes 0.208 Mid partial evidence none
SOD2 MCI 0.208 Mid partial evidence active

Depression 26

Mediator Outcome Score Tier Lit. status Trial
BDNF schizophrenia 0.312 High reproduces known active
BDNF depression severity 0.269 Mid novel signal none
BDNF major depressive disorder 0.269 Mid reproduces known active
COX-2 early treatment efficacy 0.208 Mid novel signal none
BDNF depressive phenotype 0.208 Mid novel signal none
BDNF remission 0.208 Mid reproduces known completed
BDNF depression severity (HAMD-17 score) 0.208 Mid novel signal none
BDNF improvement in depressive symptoms 0.208 Mid novel signal none
DNA methylation remission 0.208 Mid reproduces known completed
DNA methylation treatment response 0.208 Mid reproduces known completed
COX-2 social cognition performance 0.208 Mid novel signal none
DNA methylation suicidal behavior 0.208 Mid partial evidence completed
VEGF depressive symptom severity 0.208 Mid novel signal none
BDNF antidepressant treatment response 0.208 Mid novel signal none
BDNF depressive symptoms 0.208 Mid reproduces known completed
BDNF suicide risk 0.208 Mid partial evidence none
pdyn depressive symptoms 0.208 Mid reproduces known completed
BDNF depressive disorder 0.208 Mid reproduces known active
BDNF schizophrenia spectrum disorders 0.208 Mid partial evidence active
COX-2 poor antidepressant efficacy 0.208 Mid novel signal none
pdyn alcohol use disorder 0.208 Mid reproduces known completed
BDNF language function 0.208 Mid partial evidence none
BDNF visuospatial ability 0.208 Mid novel signal none
BDNF neurogenesis 0.208 Mid reproduces known none
DNA methylation major depressive disorder 0.208 Mid reproduces known active
BDNF anhedonia 0.208 Mid reproduces known none

Epilepsy 2

Mediator Outcome Score Tier Lit. status Trial
EGFR juvenile focal epilepsies 0.208 Mid novel signal none
EGFR lesional focal epilepsy 0.208 Mid novel signal none

Glioblastoma 16

Mediator Outcome Score Tier Lit. status Trial
NRF2 patient survival 0.269 Mid reproduces known completed
mTOR signaling U87mg electrotaxis 0.269 Mid novel signal none
CXCR4 tumor inflammation 0.208 Mid novel signal none
EGFR progression-free survival 0.208 Mid reproduces known none
PDYN GBM prognosis 0.208 Mid novel signal none
Twist1 astrocytoma development 0.208 Mid novel signal none
SLC44A2 GBM progression 0.208 Mid novel signal none
CXCR4 immune infiltration 0.208 Mid reproduces known none
VEGF dural arteriovenous fistula 0.208 Mid novel signal none
VEGF poor prognosis 0.208 Mid reproduces known none
Twist1 astrocytoma grade 0.208 Mid novel signal completed
GLI1 venous thromboembolism 0.208 Mid partial evidence none
galectin-3 progression to glioblastoma 0.208 Mid novel signal none
CXCR4 poor prognosis 0.208 Mid reproduces known none
VEGF shorter overall survival 0.208 Mid partial evidence none
TGFβ signaling recurrence 0.208 Mid reproduces known completed

Inflammatory bowel disease 4

Mediator Outcome Score Tier Lit. status Trial
galectin-3 inflammatory bowel diseases 0.269 Mid partial evidence none
mTOR signaling colitis 0.269 Mid reproduces known none
COX-2 inflammatory bowel disease and low grade alimentary lymphoma 0.269 Mid novel signal none
COX-2 FCEAI and histological alterations 0.208 Mid novel signal none

Multiple sclerosis 7

Mediator Outcome Score Tier Lit. status Trial
NRF2 retinal ganglion cell survival 0.269 Mid novel signal none
NRF2 visual function 0.269 Mid reproduces known completed
NRF2 Hashimoto's thyroiditis 0.269 Mid novel signal none
SLC44A2 multiple sclerosis 0.208 Mid reproduces known active
BDNF Multiple Sclerosis pathogenesis 0.208 Mid novel signal none
ERBB3 multiple sclerosis 0.208 Mid reproduces known active
ERBB3 endometriosis 0.208 Mid reproduces known none

Pancreatic cancer 30

Mediator Outcome Score Tier Lit. status Trial
PKM2 poor overall survival 0.373 High novel signal none
HDAC3 clinical stage 0.312 High partial evidence completed
HDAC3 lymph node metastasis 0.312 High partial evidence none
NRF2 poor survival 0.269 Mid reproduces known none
NRF2 5-FU resistance 0.269 Mid novel signal none
galectin-3 pancreatic cancer-associated diabetes 0.269 Mid novel signal none
β-catenin cell invasiveness 0.269 Mid partial evidence none
PKM2 poor prognosis 0.208 Mid reproduces known none
TGFβ signaling invasion 0.208 Mid reproduces known none
GLI1 liver cancer stem cell function 0.208 Mid novel signal none
CREB profibrotic inflammation 0.208 Mid novel signal none
TGFβ signaling proliferation 0.208 Mid reproduces known none
FASN prognosis 0.208 Mid reproduces known none
galectin-3 malnutrition 0.208 Mid reproduces known none
galectin-3 high hypoxia status 0.208 Mid novel signal none
galectin-3 pancreatobiliary cancer prognosis 0.208 Mid novel signal none
Wnt/β-catenin signaling pathway pancreatic ductal adenocarcinoma 0.208 Mid reproduces known none
galectin-3 pancreatobiliary cancer 0.208 Mid novel signal none
CXCR4 myofibroblast-induced invasion 0.208 Mid novel signal none
GLI1 nerve plexus density 0.208 Mid novel signal none
PKM2 unfavorable outcome 0.208 Mid partial evidence none
galectin-3 weight loss 0.208 Mid reproduces known none
FASN proliferation 0.208 Mid reproduces known none
CXCR4 differentiated phenotype 0.208 Mid novel signal none
PPARγ pancreatic cancer 0.208 Mid novel signal active
PKM2 PDAC 0.208 Mid reproduces known none
TGFβ signaling net acid extrusion 0.208 Mid novel signal none
galectin-3 insulin-stimulated glucose uptake 0.208 Mid novel signal none
HDAC2 metastasis 0.208 Mid reproduces known active
β-catenin gemcitabine sensitivity 0.208 Mid novel signal none

Rheumatoid arthritis 10

Mediator Outcome Score Tier Lit. status Trial
HDAC3 RA-ILD 0.312 High novel signal none
EGFR rheumatoid arthritis 0.269 Mid partial evidence none
COX-2 disease activity 0.269 Mid novel signal completed
NF-κB signaling pathway rheumatoid arthritis 0.269 Mid partial evidence none
COX-2 rheumatoid arthritis 0.208 Mid partial evidence none
VEGF swollen joint count 0.208 Mid novel signal none
VEGF rheumatoid arthritis 0.208 Mid partial evidence none
interferon-γ Alopecia areata 0.208 Mid novel signal completed
LAIR1 rheumatoid arthritis 0.208 Mid partial evidence none
VEGF active infection 0.208 Mid novel signal none

Type 2 diabetes 12

Mediator Outcome Score Tier Lit. status Trial
DNA methylation type 2 diabetes 0.312 High reproduces known none
galectin-3 all-cause mortality 0.269 Mid reproduces known none
Nrf2 diabetic cardiomyopathy 0.269 Mid partial evidence none
FASN NAFLD 0.269 Mid reproduces known none
DNA methylation insulin resistance 0.269 Mid reproduces known completed
galectin-3 cardiovascular events 0.269 Mid partial evidence none
SLC19A3 severe retinopathy 0.208 Mid novel signal none
FASN diabetes 0.208 Mid reproduces known completed
VEGF diabetic retinopathy 0.208 Mid partial evidence none
BDNF diabetes risk factors 0.208 Mid novel signal none
galectin-3 hypertension 0.208 Mid reproduces known completed
galectin-3 obesity 0.208 Mid reproduces known completed

Clinical trials

200 registered trials for valproic acid

Source: ClinicalTrials.gov

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