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Disulfiram

drug
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Also known as AntabuseDisulfirameEsperalNSC-25953ORA-102ORA102Bis(diethylaminethiocarbonyl)disulfideTetraethylthiuram disulfideSID11111859SID11111860SID11533044SID26747681SID26753660SID26753661SID50107088SID56422197SID85231246SID90340564Tetraethythiuran

Summary

Disulfiram (CHEMBL964) is an approved small-molecule EC 1.2.1.3 [aldehyde dehydrogenase (NAD+)] inhibitor (ATC P03AA04) targeting ALDH2 and GSDMD; indicated across 25 conditions including parasitic infectious disease and alcohol abuse.

At a glance

  • Status: Approved (max clinical phase 4)
  • Modality: Small molecule
  • ATC class: P03AA04 (+2 more)
  • Targets: 2 (ALDH2, GSDMD)
  • Indications: 25 conditions
  • Clinical trials: 53
  • Chemistry: 296.5 Da · C10H20N2S4

Identifiers

Drug identity and classification

FieldValue
ChEMBL IDCHEMBL964
NameDisulfiram
TypeSmall molecule
Max phase4
FDA approvedyes
PubChem CID3117
ChEBICHEBI:4659
ATCP03AA04, P03AA54, N07BB01
Molecular formulaC10H20N2S4
Molecular weight296.5
InChIKeyAUZONCFQVSMFAP-UHFFFAOYSA-N

SMILES: CCN(CC)C(=S)SSC(=S)N(CC)CC

IUPAC name: diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate

ChEBI definition: An organic disulfide that results from the formal oxidative dimerisation of N,N-diethyldithiocarbamic acid. A multi-enzyme inhibitor that is used in alcohol aversion therapy and also exhibits anticancer properties.

Pharmacological roles (ChEBI): EC 1.2.1.3 [aldehyde dehydrogenase (NAD+)] inhibitor, angiogenesis inhibitor, EC 3.1.1.8 (cholinesterase) inhibitor, EC 3.1.1.1 (carboxylesterase) inhibitor, EC 5.99.1.2 (DNA topoisomerase) inhibitor, fungicide, apoptosis inducer, NF-κB inhibitor, antineoplastic agent, ferroptosis inducer.

Also known as: Antabuse, Disulfiram, Disulfirame, Esperal, NSC-25953, ORA-102, ORA102, Bis(diethylaminethiocarbonyl)disulfide, Tetraethylthiuram disulfide, SID11111859, SID11111860, SID11533044

Patent coverage: 12,748 distinct patent families (38,611 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
ALDH2aldehyde dehydrogenase 2 family memberInhibition4.440.3%P05091
GSDMDgasdermin DInhibition6.43.4%P57764

Broader ChEMBL bioactivity targets: 86 (assay-derived). Sample: Pyruvate kinase PKM, Microtubule-associated protein tau, Polypyrimidine tract-binding protein 1, Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, Prelamin-A/C, Inositol monophosphatase 1, 4’-phosphopantetheinyl transferase ffp, Ferritin light chain, 15-hydroxyprostaglandin dehydrogenase [NAD(+)].

Bioactivity

ChEMBL activities: 151 potent at pChembl ≥ 5 of 205 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

TargetpChemblTypeValueUnitActivity ID
MAPT7.6Potency25.1nMCHEMBL_ACT_4516677
LOXL47.23IC5059nMCHEMBL_ACT_18676477
ALOX157.2Potency63.1nMCHEMBL_ACT_4469884
MTOR7.18Potency65.6nMCHEMBL_ACT_4522102
LMNA7.05Potency89.1nMCHEMBL_ACT_3654391
ALDH1A17.05Potency89.1nMCHEMBL_ACT_4183926
LOXL37.03IC5093nMCHEMBL_ACT_18676463
ALDH1A17Potency100nMCHEMBL_ACT_4178558
ALDH1A16.89IC50130nMCHEMBL_ACT_23203282
C7C4226.89IC50130nMCHEMBL_ACT_29253133
LOXL26.82IC50150nMCHEMBL_ACT_18676449
LMNA6.8Potency158.5nMCHEMBL_ACT_4403445
HSD17B106.8Potency158.5nMCHEMBL_ACT_4833764
HSD17B106.8Potency158.5nMCHEMBL_ACT_4861292
ALDH1A16.75Potency177.8nMCHEMBL_ACT_4167290
LMNA6.7Potency199.5nMCHEMBL_ACT_3658272
ALDH1A16.7Potency199.5nMCHEMBL_ACT_4144337
ADORA36.7Ki201nMCHEMBL_ACT_7696431
P0DTD16.66IC50220nMCHEMBL_ACT_19964271
P514506.6Potency251.2nMCHEMBL_ACT_4116550
ALDH1A16.55Potency281.8nMCHEMBL_ACT_4188214
P514506.55Potency281.8nMCHEMBL_ACT_4999635
P514506.55Potency281.8nMCHEMBL_ACT_5000462
MTOR6.53Potency293.1nMCHEMBL_ACT_4783744
LOX6.5IC50320nMCHEMBL_ACT_18676435
P514506.5Potency316.2nMCHEMBL_ACT_4798360
P514506.5Potency316.2nMCHEMBL_ACT_4995309
ADORA36.45IC50356nMCHEMBL_ACT_7696430
MGLL6.44IC50360nMCHEMBL_ACT_18449182
DRD36.43Ki368nMCHEMBL_ACT_7696513

Target pathways

Aggregated over 2 target gene(s): ALDH2, GSDMD.

Top Reactome pathways

21 total, by targets touching each:

PathwayTargetsGenes
Release of apoptotic factors from the mitochondria1GSDMD
Neurotransmitter clearance1ALDH2
Transmission across Chemical Synapses1ALDH2
Neuronal System1ALDH2
Metabolism1ALDH2
Biological oxidations1ALDH2
Phase I - Functionalization of compounds1ALDH2
Metabolism of serotonin1ALDH2
Serotonin clearance from the synaptic cleft1ALDH2
Metabolism of proteins1ALDH2
Muscle contraction1ALDH2
Smooth Muscle Contraction1ALDH2
Interleukin-1 processing1GSDMD
Pyroptosis1GSDMD
Regulation of TLR by endogenous ligand1GSDMD
Neutrophil degranulation1GSDMD
Ethanol oxidation1ALDH2
Purinergic signaling in leishmaniasis infection1GSDMD
Mitochondrial protein degradation1ALDH2
CASP4-mediated substrate cleavage1GSDMD
CASP5-mediated substrate cleavage1GSDMD

Dominant GO biological processes

GO termTargets
carbohydrate metabolic process1
alcohol metabolic process1
ethanol metabolic process1
ethanol catabolic process1
nitroglycerin metabolic process1
aldehyde catabolic process1
cellular detoxification of aldehyde1
regulation of dopamine biosynthetic process1
regulation of serotonin biosynthetic process1
plasma membrane repair1
protein secretion1
positive regulation of interleukin-1 beta production1
defense response to bacterium1
innate immune response1
ceramide biosynthetic process1

Indications & clinical

Indications

25 indications (2 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
parasitic infectious disease4MONDO:0005135EFO:0001067
alcohol abuse4MONDO:0002046MONDO:0007079
cocaine dependence2MONDO:0005186EFO:0002610
melanoma2MONDO:0005105EFO:0000756
glioblastoma2MONDO:0018177EFO:0000519
metastatic melanoma2MONDO:0005191EFO:0002617
non-small cell lung carcinoma2MONDO:0005233EFO:0003060
opiate dependence2MONDO:0005530EFO:0005611
germ cell tumor2MONDO:0005040EFO:0000514
breast neoplasm2MONDO:0021100MONDO:0007254
alcohol-related disorders2MONDO:0021698MONDO:0021698
severe acute respiratory syndrome2MONDO:0005091MONDO:0100096
exocrine pancreatic carcinoma2MONDO:0005192EFO:0002618
paraganglioma2MONDO:0000448EFO:1000453
HIV infectious disease1MONDO:0005109EFO:0000764
methamphetamine dependence1MONDO:0005419EFO:0004701
plasma cell myeloma1MONDO:0009693EFO:0001378
sarcoma1MONDO:0005089EFO:0000691
neoplasm1MONDO:0005070MONDO:0004992
inherited retinal dystrophy1MONDO:0019118MONDO:0019118
obesity disorder0MONDO:0011122EFO:0001073

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

Clinical trials

Total trials: 53.

Phase distribution

PhaseTrials
PHASE217
PHASE1/PHASE211
PHASE110
Not specified6
PHASE44
EARLY_PHASE14
PHASE2/PHASE31

Top trials by phase / activity

NCTPhaseStatusTitle
NCT00431262PHASE4UNKNOWNAntabuse in Severe Alcoholism: an Open Controlled Study
NCT00435435PHASE4COMPLETEDComparative Trial Of Disulfiram, Naltrexone And Acamprosate In The Treatment Of Alcohol Dependence
NCT02134002PHASE4WITHDRAWNA PET Exploration of the Mechanism of Action of Dopamine Beta-hydroxylase Inhibition in Cocaine Addicts
NCT02735577PHASE4COMPLETEDNeural Mechanisms of Disulfiram Effects
NCT02678975PHASE2/PHASE3COMPLETEDDisulfiram in Recurrent Glioblastoma
NCT01777919PHASE2NOT_YET_RECRUITINGDisulfiram/Copper Combination In The Treatment of Newly Diagnosed Glioblastoma Multiform
NCT03323346PHASE2RECRUITINGPhase II Trial of Disulfiram With Copper in Metastatic Breast Cancer
NCT05626920PHASE1/PHASE2RECRUITINGDisulfiram for Treatment of Retinal Degeneration
NCT07477457PHASE2RECRUITINGA Study of Gefitinib, Trametinib, Disulfiram, and Sunitinib in Addition to Standard Chemotherapy in People With Osteosarcoma
NCT07534332PHASE2NOT_YET_RECRUITINGDisulfiram in Rheumatoid Arthritis
NCT00000278PHASE2COMPLETEDDisulfiram for Cocaine-Alcohol Abuse - 3
NCT00142844PHASE2COMPLETEDCombination of Disulfiram Plus Naltrexone to Treat Both Cocaine- and Alcohol-dependent Individuals - 1
NCT00149630PHASE2COMPLETEDPharmacogenetics of Disulfiram for Cocaine
NCT00218608PHASE2COMPLETEDDisulfiram for Treating Cocaine Dependence in Individuals Maintained on Methadone
NCT00256230PHASE1/PHASE2COMPLETEDDisulfiram in Patients With Metastatic Melanoma
NCT00395850PHASE2COMPLETEDDisulfiram for Cocaine Abuse
NCT00729300PHASE1/PHASE2COMPLETEDA Study of the Relationship Between Disulfiram and Cocaine Self-administration.
NCT00731133PHASE1/PHASE2COMPLETEDOpen-Label Disulfiram for Methamphetamine Dependence
NCT00745511PHASE1/PHASE2UNKNOWNPilot Study to Evaluate the Safety and Efficacy of Treatment With ORA102 Combined With Avastin (Bevacizumab) Versus Avastin Alone, in Patients With Neovascular Age Related Macular Degeneration (AMD)
NCT00913484PHASE2COMPLETEDDisulfiram for Cocaine Abuse in Buprenorphine Treatment
NCT01944371PHASE1/PHASE2COMPLETEDShort-term Disulfiram Administration to Reverse Latent HIV Infection: a Dose Escalation Study
NCT02101008PHASE2COMPLETEDDisulfiram and Chelated Zinc for the Rx of Disseminated Mets Mel That Has Failed First Line Therapy
NCT02715609PHASE1/PHASE2COMPLETEDDisulfiram/Copper With Concurrent Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma
NCT02770378PHASE1/PHASE2COMPLETEDA Proof-of-concept Clinical Trial Assessing the Safety of the Coordinated Undermining of Survival Paths by 9 Repurposed Drugs Combined With Metronomic Temozolomide (CUSP9v3 Treatment Protocol) for Recurrent Glioblastoma
NCT03034135PHASE2COMPLETEDSafety, Tolerability and Efficacy of Disulfiram and Copper Gluconate in Recurrent Glioblastoma
NCT03198559PHASE1/PHASE2TERMINATEDCombination Latency Reversal With High Dose Disulfiram Plus Vorinostat in HIV-infected Individuals on ART
NCT03363659PHASE2TERMINATEDDisulfiram and Copper Gluconate With Temozolomide in Unmethylated Glioblastoma Multiforme
NCT03891667PHASE1/PHASE2COMPLETEDDisulfiram: A Test of Symptom Reduction Among Patients With Previously Treated Lyme Disease
NCT03950830PHASE2COMPLETEDDisulfiram and Cisplatin in Refractory TGCTs.
NCT04265274PHASE2WITHDRAWNVinorelbine, Cisplatin, Disulfiram and Copper in CTC_EMT Positive Refractory Metastatic Breast Cancer.
NCT04485130PHASE2TERMINATEDDISulfiram for COvid-19 (DISCO) Trial
NCT04502589PHASE1/PHASE2COMPLETEDOpen Label Pilot Study of Perampanel for the Treatment of Alcohol Use Disorder
NCT04594343PHASE2COMPLETEDClinical Study to Evaluate the Effects of Disulfiram in Patients With Moderate COVID-19
NCT05210374PHASE1RECRUITINGDisulfiram With Copper Gluconate and Liposomal Doxorubicin in Treatment-Refractory Sarcomas
NCT06319872PHASE1RECRUITINGThe Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT00094289PHASE1UNKNOWNInteractions Between Cocaine and Ethanol and Disulfiram - 1
NCT00350870PHASE1COMPLETEDCBT With Disulfiram and Contingency Management
NCT00571116PHASE1TERMINATEDDisulfiram Plus Arsenic Trioxide In Patients With Metastatic Melanoma and at Least One Prior Systemic Therapy
NCT00742911PHASE1COMPLETEDPhase I Study of Disulfiram and Copper Gluconate for the Treatment of Refractory Solid Tumors Involving the Liver
NCT00878306PHASE1COMPLETEDDisulfiram Interactions With HIV Medications: Clinical Implications

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 5 clinical and 13 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.

8 molecules share ≥1 primary target. Top 8 by shared-target count:

MoleculeSourceStatusShared targets
DAIDZEINChEMBLPhase 2ALDH2
DITIOCARBChEMBLPhase 2GSDMD
THIRAMChEMBLPhase 2ALDH2
CaffeinePubChemApprovedALDH2
CysteaminePubChemApprovedALDH2
DoxorubicinPubChemApprovedALDH2
GenisteinPubChemApprovedALDH2
theophyllinePubChemApprovedALDH2

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