disulfiram ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
928 97-77-8

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • disulfiram
  • tetraethylthiram disulfide
A carbamate derivative used as an alcohol deterrent. It is a relatively nontoxic substance when administered alone, but markedly alters the intermediary metabolism of alcohol. When alcohol is ingested after administration of disulfiram, blood acetaldehyde concentrations are increased, followed by flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms (acetaldehyde syndrome). It acts by inhibiting aldehyde dehydrogenase.
  • Molecular weight: 296.52
  • Formula: C10H20N2S4
  • CLOGP: 3.88
  • LIPINSKI: 0
  • HAC: 2
  • HDO: 0
  • TPSA: 6.48
  • ALOGS: -4.37
  • ROTB: 7
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.20 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 24.09 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 80 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.161 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.743 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 34.754 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 4591.980 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 4.140 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 0.800 % High 1
herg hERG pIC50 4.524 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 592.925 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 72.444 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 4.650 % High 1
kinase-safety-class ACVR2A,ACVR2B,ACVRL1,AKT2,AKT3,ALK,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK4,CDK5,CDK9,CHEK1,DDR1,DYRK1B,EGFR,EIF2AK3,EPHB4,ERBB2,FLT3,GRK2,GSK3B,IGF1R,ITK,JAK1,JAK2,JAK3,MAP2K6,MAP3K1,MAP3K14,MAP3K21,MAP3K7,MAPK1,MAPK10,MAPK7,MAPK8,MAPK9,MAPKAPK2,MARK4,MELK,MET,MTOR,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIK3CD,PIM1,PIM2,PLK1,PRKCD,PRKDC,SIK2,SIK3,STK33,SYK,TEK,TTK,ULK1,ZAP70 66
kinase-selectivity-class AXL,BRAF,CDK4,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,FGFR1,FLT4,GRK2,GSK3B,JAK2,MAP2K4,MAP2K6,MAP3K2,MAP3K7,MAPK10,MAPK12,MAPK7,MARK4,PRKDC,SGK1,STK10,STK33,SYK,TEK,TTK,UHMK1,ZAP70 31
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.031 High 1
mh-clint Mouse hepatocyte intrinsic clearance 7095.778 High 1
mppb Mouse plasma protein binding (% unbound) 21.360 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 0.004 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 9.580 % High 1
rh-clint Rat hepatocyte intrinsic clearance 473.151 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 91.900 % High 1
rppb Rat plasma protein binding (% unbound) 3.080 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 29.444 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 28, 1951 FDA

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intentional self-injury 126.85 44.01 36 1202 29298 90597911
Psychiatric symptom 119.68 44.01 26 1212 7092 90620117
Drug abuse 60.21 44.01 27 1211 82320 90544889
Drug-induced liver injury 48.68 44.01 24 1214 90294 90536915
Drug interaction 47.11 44.01 35 1203 276418 90350791

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Alcohol intolerance 137.39 31.26 23 2458 349 42618505
Milk-alkali syndrome 116.33 31.26 22 2459 685 42618169
Toxic encephalopathy 104.09 31.26 31 2450 6922 42611932
Drug abuse 83.87 31.26 60 2421 104711 42514143
Psychiatric symptom 59.52 31.26 18 2463 4223 42614631
Drug interaction 54.58 31.26 72 2409 266927 42351927
Generalised tonic-clonic seizure 49.22 31.26 26 2455 26353 42592501
Metabolic alkalosis 47.82 31.26 13 2468 2088 42616766
Bradyphrenia 43.72 31.26 15 2466 5247 42613607
Reduced facial expression 42.07 31.26 11 2470 1522 42617332
Hypertonia neonatal 40.87 31.26 9 2472 601 42618253
Hypercalcaemia 40.04 31.26 20 2461 18038 42600816
Dissociative disorder 40.00 31.26 9 2472 663 42618191
Thinking abnormal 39.21 31.26 15 2466 7146 42611708
Alcohol interaction 38.46 31.26 11 2470 2124 42616730
Intentional overdose 35.48 31.26 27 2454 51429 42567425
Acidosis hyperchloraemic 34.52 31.26 8 2473 672 42618182
Sopor 33.39 31.26 16 2465 13186 42605668
Agitation neonatal 33.26 31.26 9 2472 1419 42617435
Dissociation 32.22 31.26 11 2470 3787 42615067
Neonatal respiratory distress 31.74 31.26 8 2473 957 42617897
Mental impairment 31.37 31.26 15 2466 12302 42606552

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Psychiatric symptom 176.67 31.64 44 3506 9169 110576580
Alcohol intolerance 154.23 31.64 24 3526 423 110585326
Drug abuse 143.23 31.64 82 3468 177329 110408420
Toxic encephalopathy 115.18 31.64 35 3515 15179 110570570
Intentional self-injury 112.29 31.64 43 3507 37386 110548363
Milk-alkali syndrome 106.49 31.64 22 3528 1983 110583766
Drug interaction 89.04 31.64 94 3456 500089 110085660
Sopor 68.54 31.64 30 3520 36516 110549233
Generalised tonic-clonic seizure 65.71 31.64 33 3517 54647 110531102
Intentional overdose 60.95 31.64 43 3507 132458 110453291
Toxicity to various agents 57.95 31.64 74 3476 480481 110105268
Drug-induced liver injury 50.69 31.64 37 3513 120030 110465719
Metabolic alkalosis 42.87 31.64 13 3537 5582 110580167
Dysarthria 42.64 31.64 29 3521 84092 110501657
Dissociative disorder 39.76 31.64 9 3541 1242 110584507
Bradyphrenia 37.03 31.64 14 3536 11714 110574035
Encephalopathy 36.53 31.64 26 3524 81029 110504720
Antipsychotic drug level increased 35.95 31.64 12 3538 7003 110578746
Jarisch-Herxheimer reaction 34.62 31.64 8 3542 1209 110584540
Alcohol interaction 34.48 31.64 10 3540 3684 110582065
Psychotic disorder 34.30 31.64 21 3529 50916 110534833
Mental impairment 34.23 31.64 16 3534 22623 110563126
Hypercalcaemia 33.38 31.64 20 3530 46637 110539112
Overdose 32.92 31.64 39 3511 233755 110351994
Acidosis hyperchloraemic 32.52 31.64 8 3542 1578 110584171
Mania 32.38 31.64 15 3535 20781 110564968

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N07BB01 NERVOUS SYSTEM
OTHER NERVOUS SYSTEM DRUGS
DRUGS USED IN ADDICTIVE DISORDERS
Drugs used in alcohol dependence
ATC P03AA04 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ECTOPARASITICIDES, INCL. SCABICIDES, INSECTICIDES AND REPELLENTS
ECTOPARASITICIDES, INCL. SCABICIDES
Sulfur containing products
ATC P03AA54 ANTIPARASITIC PRODUCTS, INSECTICIDES AND REPELLENTS
ECTOPARASITICIDES, INCL. SCABICIDES, INSECTICIDES AND REPELLENTS
ECTOPARASITICIDES, INCL. SCABICIDES
Sulfur containing products
FDA MoA N0000000183 Acetyl Aldehyde Dehydrogenase Inhibitors
MeSH PA D000427 Alcohol Deterrents
MeSH PA D004791 Enzyme Inhibitors
MeSH PA D065086 Acetaldehyde Dehydrogenase Inhibitors
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:24127 fungicide
CHEBI has role CHEBI:35442 antiparasitic agent
CHEBI has role CHEBI:35487 EC 1.2.1.3 [aldehyde dehydrogenase (NAD<small><sup>+</small></sup>)] inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:37733 EC 3.1.1.8 (cholinesterase) inhibitor
CHEBI has role CHEBI:48422 angiogenesis inhibitor
CHEBI has role CHEBI:50276 EC 5.99.1.2 (DNA topoisomerase) inhibitor
CHEBI has role CHEBI:64946 anti-HIV agent
CHEBI has role CHEBI:68495 apoptosis inducer
CHEBI has role CHEBI:73240 NF-ฮบB inhibitor
CHEBI has role CHEBI:74518 anti-obesity agent
CHEBI has role CHEBI:78444 EC 3.1.1.1 (carboxylesterase) inhibitor
CHEBI has role CHEBI:173085 ferroptosis inducer
FDA EPC N0000175679 Aldehyde Dehydrogenase Inhibitor

Related Drugs by ATC class:

N07BB Drugs used in alcohol dependence 4 drugs
acamprosatecalcium carbimidenalmefenenaltrexone
P03AA Sulfur containing products 3 drugs
dixanthogenmesulfenthiram

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Alcoholism indication 7200002
Cirrhosis of liver contraindication 19943007 DOID:5082
Chronic glomerulonephritis contraindication 20917003
Alcohol intoxication contraindication 25702006
Hypothyroidism contraindication 40930008 DOID:1459
Conduction disorder of the heart contraindication 44808001
Chronic heart failure contraindication 48447003
Nephritis contraindication 52845002 DOID:10952
Coronary arteriosclerosis contraindication 53741008 DOID:3393
Psychotic disorder contraindication 69322001
Diabetes mellitus contraindication 73211009 DOID:9351
Epilepsy contraindication 84757009 DOID:1826
Disease of liver contraindication 235856003 DOID:409
Cognitive Impairment following Traumatic Brain Injury contraindication




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

None

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Aldehyde dehydrogenase, mitochondrial Enzyme INHIBITOR IC50 5.47 CHEMBL CHEMBL
Amine oxidase [flavin-containing] A Enzyme IC50 4.86 DRUG MATRIX
Fructose-1,6-bisphosphatase 1 Enzyme IC50 6.22 CHEMBL
Sodium/nucleoside cotransporter 1 Transporter Ki 5.24 DRUG MATRIX
Mu-type opioid receptor GPCR Ki 5.85 DRUG MATRIX
Translocator protein Transporter WOMBAT-PK
D(1A) dopamine receptor GPCR Ki 5.97 DRUG MATRIX
D(2) dopamine receptor GPCR Ki 5.12 DRUG MATRIX
Alpha-2A adrenergic receptor GPCR Ki 5.74 DRUG MATRIX
Sodium-dependent noradrenaline transporter Transporter Ki 4.16 DRUG MATRIX
5-hydroxytryptamine receptor 2B GPCR Ki 4.66 DRUG MATRIX
5-hydroxytryptamine receptor 6 GPCR Ki 5.13 DRUG MATRIX
Alpha-2B adrenergic receptor GPCR Ki 5.83 DRUG MATRIX
D(3) dopamine receptor GPCR Ki 6.43 DRUG MATRIX
Sodium-dependent dopamine transporter Transporter Ki 5.43 DRUG MATRIX
Adenosine receptor A3 GPCR Ki 6.70 DRUG MATRIX
D(4) dopamine receptor GPCR Ki 5.96 DRUG MATRIX
Kappa-type opioid receptor GPCR Ki 5.61 DRUG MATRIX
Retinal dehydrogenase 1 Enzyme IC50 6.89 CHEMBL
cAMP-specific 3',5'-cyclic phosphodiesterase 4A Enzyme IC50 5.32 DRUG MATRIX
C-C chemokine receptor type 5 GPCR Ki 4.74 DRUG MATRIX
C-X-C chemokine receptor type 2 GPCR Ki 5.38 DRUG MATRIX
C-C chemokine receptor type 2 GPCR Ki 6.02 DRUG MATRIX
Mitogen-activated protein kinase 3 Kinase IC50 5.82 DRUG MATRIX
C-C chemokine receptor type 4 GPCR Ki 5.36 DRUG MATRIX
Monoglyceride lipase Enzyme IC50 5.90 CHEMBL
Protein-lysine 6-oxidase Enzyme IC50 6.50 CHEMBL
Lysine-specific demethylase 5A Enzyme IC50 5 CHEMBL
Lysyl oxidase homolog 3 Enzyme IC50 7.03 CHEMBL
Lysyl oxidase homolog 4 Enzyme IC50 7.23 CHEMBL
Histone-lysine N-methyltransferase EHMT2 Enzyme IC50 6.22 CHEMBL
Histone-lysine N-methyltransferase EHMT1 Enzyme IC50 5.80 CHEMBL
Lysyl oxidase homolog 2 Enzyme IC50 6.82 CHEMBL
Gasdermin-D Membrane other IC50 6.40 CHEMBL
Cytochrome P450 1A2 Enzyme IC50 5.40 DRUG MATRIX
Arachidonate 15-lipoxygenase Enzyme IC50 4.79 DRUG MATRIX
5-hydroxytryptamine receptor 1B GPCR Ki 5.67 DRUG MATRIX
Membrane-associated progesterone receptor component 1 Membrane receptor Ki 4.33 DRUG MATRIX
Aldehyde dehydrogenase, mitochondrial Enzyme IC50 4.40 CHEMBL
Bifunctional protein GlmU Enzyme IC50 4.07 CHEMBL
Beta-lactamase NDM-1 Enzyme IC50 6.89 CHEMBL
Replicase polyprotein 1ab Enzyme IC50 5.98 CHEMBL
NACHT, LRR and PYD domains-containing protein 3 Cytosolic other IC50 5.52 CHEMBL
Gasdermin-D Membrane other IC50 6.40 CHEMBL
Carbamate kinase, EC 2.7.2.2 Kinase IC50 6.22 CHEMBL

External reference:

IDSource
4018494 VUID
N0000146816 NUI
D00131 KEGG_DRUG
3554 RXNORM
4018494 VANDF
C0012772 UMLSCUI
CHEBI:4659 CHEBI
CHEMBL964 ChEMBL_ID
DB00822 DRUGBANK_ID
D004221 MESH_DESCRIPTOR_UI
3117 PUBCHEM_CID
7168 IUPHAR_LIGAND_ID
1781 INN_ID
TR3MLJ1UAI UNII
2848 MMSL
4623 MMSL
d01389 MMSL
000752 NDDF
387212009 SNOMEDCT_US
39516004 SNOMEDCT_US
TR3MLJ1UAI INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 42794-028 TABLET 250 mg ORAL ANDA 17 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 42794-029 TABLET 500 mg ORAL ANDA 17 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 47781-607 TABLET 250 mg ORAL ANDA 18 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 47781-607 TABLET 250 mg ORAL ANDA 18 sections
Antabuse HUMAN PRESCRIPTION DRUG LABEL 1 54868-5034 TABLET 250 mg ORAL ANDA 18 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 60429-196 TABLET 250 mg ORAL ANDA 17 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 62135-431 TABLET 250 mg ORAL ANDA 13 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 62135-432 TABLET 500 mg ORAL ANDA 13 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 63629-5466 TABLET 250 mg ORAL ANDA 17 sections
Disulfiram HUMAN PRESCRIPTION DRUG LABEL 1 68151-2694 TABLET 250 mg ORAL ANDA 17 sections