Details of the Drug

General Information of Drug (ID: DMCL2OK)

Drug Name

Disulfiram

Synonyms

Abstenisil; Abstinil; Abstinyl; Alcophobin; Antabus; Antabuse; Antadix; Antaenyl; Antaethan; Antaethyl; Antaetil; Antalcol; Antetan; Antethyl; Antetil; Anteyl; Anthethyl; Antiaethan; Anticol; Antietanol; Antiethanol; Antietil; Antikol; Antivitium; Aversan; Averzan; Bonibal; Contralin; Contrapot; Cronetal; Dicupral; Disetil; Disulfan; Disulfirame; Disulfiramo; Disulfiramum; Disulfirm; Disulfram; Disulfuram; Disulphuram; Ephorran; Espenal; Esperal; Etabus; Ethyldithiourame; Ethyldithiurame; Exhoran; Exhorran; Gababentin; Hoca; Krotenal; Nocbin; Nocceler; Noxal; Refusal; Stopaethyl; Stopethyl; Stopety; Stopetyl; TATD; TETD; THIOCID; TTD; TTS; Tenurid; Tenutex; Tetidis; Tetradin; Tetradine; Tetraethylthiuram; Tetraetil; Teturam; Teturamin; Thireranide; Thiuranide; Tillram; Tiuram; Accel TET; Akrochem TETD; Ancazide ET; Antab use; Disulfirame [DCIT]; Ekagom DTET; Ekagom TEDS; Ekagom TETDS; Ekaland TETD; Esperal [France]; Eta bus; Ethyl Thiram; Ethyl Thiudad; Ethyl Thiurad; Ethyl Tuads Rodform; Ethyl Tuex; Ethyl tuads; Etyl Tuex; Nocceler TET; Perkacit TETD; Perkait TETD; Robac TET; Sanceler TET; Soxinol TET; TTS x; Tet raethylthiuram; Thiuram E; Dupon 4472; T 1132; Accel TET-R; Alk-aubs; Antabus (TN); Antabuse (TN); Anti-ethyl; Antivitium (Spain); ENT 27,340; Nocceler TET-G; Noxal (VAN); Ro-sulfiram; Sanceler TET-G; Tuads, ethyl; Usaf B-33; Ro-Sulfram-500 (USA)

Indication

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[1]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[2]
Middle East Respiratory Syndrome (MERS)	1D64	Investigative	[3]
Severe acute respiratory syndrome (SARS)	1D65	Investigative	[3]
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Therapeutic Class

Alcohol Deterrents

Drug Type

Small molecular drug

Structure

3D MOL

2D MOL

#Ro5 Violations (Lipinski): 0

Molecular Weight (mw)

296.5

Logarithm of the Partition Coefficient (xlogp)

3.9

Rotatable Bond Count (rotbonds)

Hydrogen Bond Donor Count (hbonddonor)

Hydrogen Bond Acceptor Count (hbondacc)

ADMET Property

BDDCS Class: Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 2: low solubility and high permeability [4]
Bioavailability: 80% of drug becomes completely available to its intended biological destination(s) [5]
Elimination: 0% of drug is excreted from urine in the unchanged form [4]
MRTD: The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 24.0873 micromolar/kg/day [6]
Water Solubility: The ability of drug to dissolve in water is measured as 0.2 mg/mL [4]

Adverse Drug Reaction (ADR)

ADR Term	Variation	Related DOT	DOT ID	REF
Dyspnoeas	Not Available	ALDH1A3	OT1C9NKQ	[7]
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Chemical Identifiers

Formula: C10H20N2S4
IUPAC Name: diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
Canonical SMILES: CCN(CC)C(=S)SSC(=S)N(CC)CC
InChI: InChI=1S/C10H20N2S4/c1-5-11(6-2)9(13)15-16-10(14)12(7-3)8-4/h5-8H2,1-4H3
InChIKey: AUZONCFQVSMFAP-UHFFFAOYSA-N

Cross-matching ID

PubChem CID: 3117
ChEBI ID: CHEBI:4659
CAS Number: 97-77-8
DrugBank ID: DB00822
TTD ID: D0X5SD
VARIDT ID: DR00310
INTEDE ID: DR0519
ACDINA ID: D00206

Combinatorial Drugs (CBD)

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Repurposed Drugs (RPD)

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Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Fatty aldehyde dehydrogenase (ALDH3A2)	TTB6UM0	AL3A2_HUMAN	Inhibitor	[8]
COVID-19 papain-like proteinase (PL-PRO)	TTNHMO8	R1AB_SARS2 (819-2763)	Inhibitor	[2]
MERS-CoV papain-like proteinase (PL-PRO)	TTYJOLE	R1AB_CVEMC (854-2740)	Inhibitor	[3]
SARS-CoV papain-like proteinase (PL-PRO)	TTRGHB2	R1AB_CVHSA (819-2740)	Inhibitor	[3]

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Drug-Metabolizing Enzyme (DME)

DME Name	DME ID	UniProt ID	MOA	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Substrate	[9]
Cytochrome P450 2E1 (CYP2E1)	DEVDYN7	CP2E1_HUMAN	Substrate	[10]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Substrate	[11]

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Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
11-beta-hydroxysteroid dehydrogenase type 2 (HSD11B2)	OTHF4H9U	DHI2_HUMAN	Gene/Protein Processing	[12]
6-phosphogluconate dehydrogenase, decarboxylating (PGD)	OTVG296F	6PGD_HUMAN	Gene/Protein Processing	[13]
72 kDa type IV collagenase (MMP2)	OT5NIWA2	MMP2_HUMAN	Gene/Protein Processing	[14]
Aldehyde dehydrogenase 1A1 (ALDH1A1)	OTCUWZKB	AL1A1_HUMAN	Gene/Protein Processing	[15]
Aldehyde dehydrogenase, dimeric NADP-preferring (ALDH3A1)	OTAYZZE6	AL3A1_HUMAN	Regulation of Drug Effects	[16]
Aldehyde dehydrogenase, mitochondrial (ALDH2)	OTKJ9I3N	ALDH2_HUMAN	Gene/Protein Processing	[17]
Aldo-keto reductase family 1 member B1 (AKR1B1)	OTRX72TH	ALDR_HUMAN	Gene/Protein Processing	[13]
Aldo-keto reductase family 1 member B10 (AKR1B10)	OTOA4HTH	AK1BA_HUMAN	Gene/Protein Processing	[13]
Aldo-keto reductase family 1 member C1 (AKR1C1)	OTQKR4CM	AK1C1_HUMAN	Gene/Protein Processing	[13]
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Gene/Protein Processing	[13]

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Molecular Interaction Atlas (MIA)

MIA Detail

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Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Disulfiram (Comorbidity)

DDI Drug Name	DDI Drug ID	Severity	Mechanism	Comorbidity	REF
Remdesivir	DMBFZ6L	Moderate	Increased risk of hepatotoxicity by the combination of Disulfiram and Remdesivir.	1D6YCoronavirus Disease 2019 [1D6YCoronavirus Disease 2019]	[18]
Bedaquiline	DM3906J	Moderate	Increased risk of hepatotoxicity by the combination of Disulfiram and Bedaquiline.	Antimicrobial drug resistance [MG50-MG52]	[19]
Aminophylline	DML2NIB	Moderate	Decreased metabolism of Disulfiram caused by Aminophylline mediated inhibition of CYP450 enzyme.	Asthma [CA23]	[20]
Pexidartinib	DMS2J0Z	Major	Increased risk of hepatotoxicity by the combination of Disulfiram and Pexidartinib.	Bone/articular cartilage neoplasm [2F7B]	[21]
Oxtriphylline	DMLHSE3	Moderate	Decreased metabolism of Disulfiram caused by Oxtriphylline mediated inhibition of CYP450 enzyme.	Cough [MD12]	[20]
Sertraline	DM0FB1J	Major	Decreased metabolism of Disulfiram caused by Sertraline mediated inhibition of non-CYP450 enzyme.	Depression [6A70-6A7Z]	[22]
Fosphenytoin	DMOX3LB	Moderate	Decreased metabolism of Disulfiram caused by Fosphenytoin mediated inhibition of CYP450 enzyme.	Epilepsy/seizure [8A61-8A6Z]	[23]
Isoniazid	DM5JVS3	Moderate	Additive dopaminergic effects by the combination of Disulfiram and Isoniazid.	HIV-infected patients with tuberculosis [1B10-1B14]	[24]
Brentuximab vedotin	DMWLC57	Moderate	Increased risk of peripheral neuropathy by the combination of Disulfiram and Brentuximab vedotin.	Hodgkin lymphoma [2B30]	[25]
Tipranavir	DM8HJX6	Major	Decreased metabolism of Disulfiram caused by Tipranavir mediated inhibition of non-CYP450 enzyme.	Human immunodeficiency virus disease [1C60-1C62]	[26]
Zalcitabine	DMH7MUV	Moderate	Increased risk of peripheral neuropathy by the combination of Disulfiram and Zalcitabine.	Human immunodeficiency virus disease [1C60-1C62]	[27]
Abacavir	DMMN36E	Minor	Increased plasma concentrations of Disulfiram and Abacavir due to competitive inhibition of the same metabolic pathway.	Human immunodeficiency virus disease [1C60-1C62]	[28]
Mipomersen	DMGSRN1	Major	Increased risk of hepatotoxicity by the combination of Disulfiram and Mipomersen.	Hyper-lipoproteinaemia [5C80]	[29]
Teriflunomide	DMQ2FKJ	Major	Increased risk of hepatotoxicity by the combination of Disulfiram and Teriflunomide.	Hyper-lipoproteinaemia [5C80]	[30]
BMS-201038	DMQTAGO	Major	Increased risk of hepatotoxicity by the combination of Disulfiram and BMS-201038.	Hyper-lipoproteinaemia [5C80]	[31]
Pirfenidone	DM6VZFQ	Moderate	Decreased metabolism of Disulfiram caused by Pirfenidone mediated inhibition of CYP450 enzyme.	Idiopathic interstitial pneumonitis [CB03]	[32]
Paraldehyde	DMOC1BX	Major	Decreased metabolism of Disulfiram caused by Paraldehyde mediated inhibition of non-CYP450 enzyme.	Insomnia [7A00-7A0Z]	[18]
Calaspargase pegol	DMQZBXI	Moderate	Increased risk of hepatotoxicity by the combination of Disulfiram and Calaspargase pegol.	Malignant haematopoietic neoplasm [2B33]	[33]
Idelalisib	DM602WT	Moderate	Increased risk of hepatotoxicity by the combination of Disulfiram and Idelalisib.	Mature B-cell leukaemia [2A82]	[34]
Vemurafenib	DM62UG5	Moderate	Decreased metabolism of Disulfiram caused by Vemurafenib mediated inhibition of CYP450 enzyme.	Melanoma [2C30]	[18]
Thalidomide	DM70BU5	Moderate	Increased risk of peripheral neuropathy by the combination of Disulfiram and Thalidomide.	Multiple myeloma [2A83]	[27]
Leflunomide	DMR8ONJ	Major	Increased risk of hepatotoxicity by the combination of Disulfiram and Leflunomide.	Rheumatoid arthritis [FA20]	[30]
Vardenafil	DMTBGW8	Moderate	Decreased metabolism of Disulfiram caused by Vardenafil mediated inhibition of CYP450 enzyme.	Sexual dysfunction [HA00-HA01]	[35]
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⏷ Show the Full List of 23 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG

DIG Name	DIG ID	PubChem CID	Functional Classification
Stearic acid	E00079	5281	Emulsifying agent; Solubilizing agent; Viscosity-controlling agent; lubricant
Beta-D-lactose	E00099	6134	Diluent; Dry powder inhaler carrier; Lyophilization aid
Carmellose sodium	E00625	Not Available	Disintegrant
Crospovidone	E00626	Not Available	Disintegrant
Lactose monohydrate	E00393	104938	Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate	E00208	11177	lubricant
Poloxamer 188	E00645	Not Available	Emulsifying agent; Solubilizing agent; Surfactant
Povidone	E00667	Not Available	Binding agent; Coating agent; Disintegrant; Film/membrane-forming agent; Solubilizing agent; Suspending agent
Silicon dioxide	E00670	Not Available	Anticaking agent; Opacifying agent; Viscosity-controlling agent
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⏷ Show the Full List of 9 Pharmaceutical Excipients of This Drug

Pharmaceutical Formulation

Formulation Name	Drug Dosage	Dosage Form	Route
Disulfiram 250 mg tablet	250 mg	Oral Tablet	Oral
Disulfiram 500 mg tablet	500 mg	Oral Tablet	Oral

Jump to Detail Pharmaceutical Formulation Page of This Drug

References

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2	Structure of Mpro from COVID-19 virus and discovery of its inhibitors. Nature. 2020 Apr 9.
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10	Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans. J Pharmacol Exp Ther. 1999 Oct;291(1):213-9.
11	Identification of the human P-450 enzymes responsible for the sulfoxidation and thiono-oxidation of diethyldithiocarbamate methyl ester: role of P-450 enzymes in disulfiram bioactivation. Alcohol Clin Exp Res. 1998 Sep;22(6):1212-9.
12	Species-specific differences in the inhibition of human and zebrafish 11beta-hydroxysteroid dehydrogenase 2 by thiram and organotins. Toxicology. 2012 Nov 15;301(1-3):72-8.
13	Keratinocyte gene expression profiles discriminate sensitizing and irritating compounds. Toxicol Sci. 2010 Sep;117(1):81-9.
14	Disulfiram suppresses invasive ability of osteosarcoma cells via the inhibition of MMP-2 and MMP-9 expression. J Biochem Mol Biol. 2007 Nov 30;40(6):1069-76. doi: 10.5483/bmbrep.2007.40.6.1069.
15	The interaction of disulfiram and H(2)S metabolism in inhibition of aldehyde dehydrogenase activity and liver cancer cell growth. Toxicol Appl Pharmacol. 2021 Sep 1;426:115642. doi: 10.1016/j.taap.2021.115642. Epub 2021 Jul 6.
16	Contribution of aldehyde dehydrogenase 3A1 to disulfiram penetration through monolayers consisting of cultured human corneal epithelial cells. Biol Pharm Bull. 2008 Jul;31(7):1444-8. doi: 10.1248/bpb.31.1444.
17	The enzymatic activity of human aldehyde dehydrogenases 1A2 and 2 (ALDH1A2 and ALDH2) is detected by Aldefluor, inhibited by diethylaminobenzaldehyde and has significant effects on cell proliferation and drug resistance. Chem Biol Interact. 2012 Jan 5;195(1):52-60.
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29	Product Information. Kynamro (mipomersen). Genzyme Corporation, Cambridge, MA.
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