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Drug-Target Interaction

Drug

show drug details
PubChem ID:3117
Structure:
Synonyms:
1,1',1'',1'''-[disulfanediylbis(carbonothioylnitrilo)]tetraethane
1,1',1'',1'''-[dithiobis(carbonothioylnitrilo)]tetraethane
1,1'-Dithiobis(N,N-diethylthioformamide)
1,1'-Dithiobis[N,N-diethylthioformamide]
11078-22-1
155-01-1
86720_ALDRICH
86720_FLUKA
97-77-8
AB00051976
Abstenisil
Abstensil
Abstensyl (Argentina)
Abstinil
Abstinyl
AC1L1F7H
AC1Q2YXI
Accel TET
Accel TET-R
AI3-27340
AIDS-010293
AIDS010293
AKOS000120201
Akrochem TETD
Alcophobin
Alk-Aubs
Allphar Brand of Disulfiram
Altana Pharma Brand of Disulfiram
Ancazide ET
Antab use
Antabus
Antabuse
Antabuse (TN)
Antabuse, Antabus, Disulfiram
Antadix
Antaenyl
Antaethan
Antaethyl
Antaetil
Antalcol
Antetan
Antethyl
Antetil
Anteyl
Anthethyl
anti-Ethyl
Antiaethan
Anticol
Antietanol
Antiethanol
Antietil
Antikol
Antivitium
Antivitium (Spain)
ARONIS24121
Artu Brand of Disulfiram
Aversan
Averzan
B0479
Bis((diethylamino)thioxomethyl) disulfide
bis((diethylamino)thioxomethyl)disulfide
Bis((diethylamino)thioxomethyl)disulphide
Bis(diethylthiocarbamoyl) disulfide
Bis(diethylthiocarbamoyl)disulphide
Bis(diethylthiocarbamyl) disulfide
Bis(N,N-diethylthiocarbamoyl) disulfide
Bis(N,N-diethylthiocarbamoyl)disulphide
bis-(diethylthiocarbamoyl)disulfide
Bis[(diethylamino)thioxomethyl] disulfide
Bohm Brand of Disulfiram
Bonibal
BPBio1_000060
BRD-K32744045-001-05-6
BSPBio_000054
BSPBio_001930
C01692
C10H20N2S4
CAS-97-77-8
CCG-39549
CCRIS 582
CHEBI:4659
CHEMBL964
Contralin
Contrapot
CPD000059171
Cronetal
D00131
D004221
DB00822
Dicupral
diethylcarbamothioylsulfanyl diethylaminomethanedithioate
diethylcarbamothioylsulfanyl N,N-diethylcarbamodithioate
Disetil
Disulfamide
Disulfan
Disulfide, bis(diethylthiocarbamoyl)
Disulfide, Tetraethylthiuram
Disulfiram
Disulfiram (JP15/USP/INN)
Disulfiram (JP16/USP/INN)
DISULFIRAM (TETRAETHYLTHIURAM DISULFIDE)
Disulfiram [BAN:INN:JAN]
Disulfiram [INN:BAN:JAN]
Disulfiram-Supplied by Selleck Chemicals
Disulfirame
Disulfirame [DCIT]
Disulfiramo
Disulfiramo [INN-Spanish]
Disulfiramum
Disulfiramum [INN-Latin]
Disulfirm
Disulfram
Disulfuram
Disulphuram
DRG-0068
Dumex Brand of Disulfiram
Dupon 4472
Dupont fungicide 4472
EINECS 202-607-8
Ekagom DTET
Ekagom TEDS
Ekagom TETDS
Ekaland TETD
ENT 27,340
Ephorran
Espenal
Esperal
Esperal [France]
Eta bus
Etabus
Ethyl Thiram
Ethyl Thiudad
Ethyl Thiurad
Ethyl tuads
Ethyl Tuads Rodform
Ethyl Tuex
Ethyldithiourame
Ethyldithiurame
Etyl Tuex
EU-0101164
Exhoran
Exhorran
Formamide, 1,1'-dithiobis(N,N-diethylthio)-
Formamide, 1,1'-dithiobis(N,N-diethylthio-
Gababentin
HMS1568C16
HMS1920I16
HMS2051M17
HMS2090C18
HMS2091O22
HMS2095C16
HMS2230K06
HMS3263J09
Hoca
Hocakrotenalnci-C02959
HSDB 3317
KBio2_001490
KBio2_004058
KBio2_006626
KBio3_001150
KBioGR_000895
KBioSS_001490
Krotenal
Lopac-T-1132
Lopac0_001164
LS-2031
MLS000069818
MLS000758264
MLS001076475
N,N,N',N'-Tetraethylthiuram disulfide
N,N,N',N'-Tetraethylthiuram disulphide
NCGC00016000-01
NCGC00016000-02
NCGC00016000-03
NCGC00016000-04
NCGC00016000-05
NCGC00016000-06
NCGC00016000-07
NCGC00016000-08
NCGC00016000-09
NCGC00016000-10
NCGC00016000-11
NCGC00016000-12
NCGC00016000-13
NCGC00016000-14
NCGC00016000-15
NCGC00094423-01
NCGC00094423-02
NCGC00094423-03
NCGC00094423-05
NCGC00094423-06
NCGC00094423-07
nchembio.559-comp2
NCI-C02959
Nocbin
Nocceler
Nocceler TET
Nocceler TET-G
Noxal
Noxal (VAN)
NSC 190940
NSC 25953
NSC-25953
NSC25953
Odyssey Brand of Disulfiram
Orphan Brand of Disulfiram
Perkacit TETD
Perkait TETD
Prestwick0_000097
Prestwick1_000097
Prestwick2_000097
Prestwick3_000097
Prestwick_182
Refusal
Refusal [Netherlands]
Ro-Sulfiram
Ro-Sulfram-500 (USA)
Robac TET
S00294
S1680_Selleck
SAM001247028
Sanceler TET
Sanceler TET-G
Sanofi Synthelabo Brand of Disulfiram
SBB058706
SMR000059171
Soxinol TET
SPBio_001191
SPBio_001993
SPECTRUM1500262
Spectrum2_001176
Spectrum3_000405
Spectrum4_000228
Spectrum5_001590
Spectrum_001010
STL069539
Stopaethyl
Stopethyl
Stopety
Stopetyl
T 1132
T1132_SIGMA
TATD
Tenurid
Tenutex
tet raethylthiuram
TETD
Tetidis
Tetradin
Tetradine
Tetraethylthioperoxydicarbonic diamide
Tetraethylthioperoxydicarbonic Diamide, ((H2N)C(S))2S2
Tetraethylthioperoxydicarbonothioic Diamide
Tetraethylthiram disulfide
Tetraethylthiram disulphide
Tetraethylthiuram
Tetraethylthiuram disulfide
Tetraethylthiuram disulphide
Tetraethylthiuram sulfide
Tetraethylthiuran disulfide
Tetraethylthiurium disulfide
Tetraetil
Teturam
Teturamin
Thiocid
Thioperoxydicarbonic diamide (((H2N)C(S))2S2), N,N,N',N'-tetraethyl-
Thioperoxydicarbonic diamide (((H2N)C(S))2S2), tetraethyl-
Thioperoxydicarbonic diamide ((H2N)C(S))2S2, tetraethyl-
Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), N,N,N',N'-tetraethyl-
Thioperoxydicarbonic diamide ([(H2N)C(S)]2S2), tetraethyl-
Thioperoxydicarbonic diamide, tetraethyl-
Thiosan
Thioscabin
Thireranide
Thiuram disulfide, tetraethyl-
Thiuram E
Thiuranide
Tillram
Tiuram
TTD
TTS
TTS x
TTS [Alcohol deterrent]
Tuads, ethyl
UNII-TR3MLJ1UAI
UPCMLD-DP090
UPCMLD-DP090:001
Usaf B-33
WLN: 2N2 & YUS & S 2
ZINC01529266
ATC-Codes:
Side-Effects:
Side-EffectFrequency
hepatitis0
neuritis0
peripheral neuropathy0
polyneuritis0
psychosis0
hepatic failure0
impotence0
optic neuritis0
atopic dermatitis0
somnolence0
headache0

Target

show target details
Uniprot ID:CP2E1_HUMAN
Synonyms:
4-nitrophenol 2-hydroxylase
CYPIIE1
Cytochrome P450 2E1
P450-J
EC-Numbers:1.14.13.-
1.14.13.n7
Organism:Homo sapiens
Human
PDB IDs:3E4E 3E6I
Structure:
3E6I

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----
----
----
----
----
----
----
----
----
----
----
----

References:

008870687
012781212
10078678
Clinical isoflurane metabolism by cytochrome P450 2E1.. E D Kharasch; D C Hankins; K Cox (1999) Anesthesiology display abstract
BACKGROUND: Some evidence suggests that isoflurane metabolism to trifluoroacetic acid and inorganic fluoride by human liver microsomes in vitro is catalyzed by cytochrome P450 2E1 (CYP2E1). This investigation tested the hypothesis that P450 2E1 predominantly catalyzes human isoflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. METHODS: Twenty-two elective surgery patients who provided institutionally-approved written informed consent were randomized to receive disulfiram (500 mg orally, N = 12) or nothing (controls, N = 10) the evening before surgery. All patients received a standard isoflurane anesthetic (1.5% end-tidal in oxygen) for 8 hr. Urine and plasma trifluoroacetic acid and fluoride concentrations were quantitated in samples obtained for 4 days postoperatively. RESULTS: Patient groups were similar with respect to age, weight, gender, duration of surgery, blood loss, and delivered isoflurane dose, measured by cumulative end-tidal isoflurane concentrations (9.7-10.2 MAC-hr). Postoperative urine excretion of trifluoroacetic acid (days 1-4) and fluoride (days 1-3) was significantly (P
10348802
10490907
Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans.. M G Emery; C Jubert; K E Thummel; E D Kharasch (1999) The Journal of pharmacology and experimental therapeutics display abstract
Disulfiram (DSF) is a mechanism-based inhibitor of cytochrome P-450 2E1 (CYP2E1), resulting in loss of CYP2E1 protein and activity, which may be useful in preventing CYP2E1-mediated xenobiotic toxicity. The duration of inhibition after a single DSF dose is, however, unknown. The purpose of this investigation was to determine this duration, and CYP2E1 formation and degradation rates, in humans. Oral chlorzoxazone (CLZ) was used as the selective in vivo probe for CYP2E1. Healthy subjects received CLZ to determine baseline CYP2E1 activity (CLZ plasma clearance and 6-hydroxychlorzoxazone fractional metabolic clearance). One week later, DSF (500 mg orally) was administered at bedtime, and CLZ administered the following morning and 3, 6, 8, 10, and 13 days after DSF. A terminal DSF metabolite, 2-thiothiazolidine-4 carboxylic acid, was also measured in each 24-h urine sample. The mean CLZ clearance and 6-hydroxychlorzoxazone fractional metabolic clearance on the first day declined to 10.2 and 5.5% of baseline values, indicating rapid and profound CYP2E1 inhibition. CYP2E1 activity returned to half that of control on day 3, and to baseline values on day 8. Assuming zero-order synthesis and first-order degradation, the in vivo CYP2E1 synthesis rate and degradation half-life was estimated to be 11 +/- 5 nmol/h and 50 +/- 19 h, respectively. Significant amounts of 2-thiothiazolidine-4 carboxylic acid were present only on day 1, suggesting that the return of in vivo CYP2E1 activity was not caused by inhibitor washout, but by enzyme resynthesis. Results regarding CYP2E1 disposition may be useful for modeling the effects of CYP2E1 inducers and inhibitors. For prevention of CYP2E1-mediated bioactivation, depending on protoxicant disposition, a second DSF dose might be necessary to completely prevent toxicity.
7793652
8162670
Clinical enflurane metabolism by cytochrome P450 2E1.. E D Kharasch; K E Thummel; D Mautz; S Bosse (1994) Clinical pharmacology and therapeutics display abstract
BACKGROUND: Fluorinated ether anesthetic hepatotoxicity and nephrotoxicity are mediated by cytochrome P450-catalyzed oxidative metabolism. Metabolism of the volatile anesthetic enflurane to inorganic fluoride ion by human liver microsomes in vitro is catalyzed predominantly by the cytochrome P450 isoform CYP2E1. This investigation tested the hypothesis that P450 2E1 is also the isoform responsible for human enflurane metabolism in vivo. Disulfiram, which is converted in vivo to a selective inhibitor of P450 2E1, was used as a metabolic probe for P450 2E1. METHODS: Twenty patients undergoing elective surgery were randomized to receive disulfiram (500 mg orally; n = 10) or nothing (control subjects; n = 10) the evening before surgery. All patients received a standard anesthetic of enflurane (2.2% end-tidal) in oxygen for 3 hours. Blood enflurane concentrations were measured by gas chromatography. Plasma and urine fluoride concentrations were quantitated by ion-selective electrode. RESULTS: Patient groups were similar with respect to age, weight, gender, duration of surgery, and blood loss. Total enflurane dose, measured by cumulative end-tidal enflurane concentrations (3.9 to 4.1 MAC-hr) and by blood enflurane concentrations, was similar in both groups. Plasma fluoride concentrations increased from 3.6 +/- 1.5 mumol/L (baseline) to 24.3 +/- 3.8 mumol/L (peak) in untreated patients (mean +/- SE). Disulfiram treatment completely abolished the rise in plasma fluoride concentration. Urine fluoride excretion was similarly significantly diminished in disulfiram-treated patients. Fluoride excretion in disulfiram-treated patients was 62 +/- 10 and 61 +/- 12 mumol on days 1 and 2, respectively, compared with 1090 +/- 180 and 1200 +/- 220 mumol in control subjects (p < 0.05 on each day). CONCLUSIONS: Disulfiram prevented fluoride ion production after enflurane anesthesia. These results suggest that P450 2E1 is the predominant P450 isoform responsible for human clinical enflurane metabolism in vivo.
8390837
8513656
Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1.. E D Kharasch; K E Thummel; J Mhyre; J H Lillibridge (1993) Clinical pharmacology and therapeutics display abstract
Disulfiram and its reduced metabolite diethyldithiocarbamate have been identified previously as selective mechanism-based inhibitors of human liver microsomal cytochrome P450 2E1 in vitro. In animals, a single oral dose of disulfiram has been shown to produce a rapid and selective inactivation of hepatic P450 2E1 content and catalytic activity in vivo. This investigation explored the efficacy of single dose disulfiram as an inhibitor of human P450 2E1 activity in vivo. Clinical P450 2E1 activity was assessed by the 6-hydroxylation of chlorzoxazone, a metabolic pathway catalyzed selectively by P450 2E1. Six healthy volunteers received 750 mg oral chlorzoxazone on two occasions in a crossover design, 10 hours after 500 mg oral disulfiram, or after no pretreatment (control subjects). Disulfiram pretreatment markedly decreased chlorzoxazone elimination clearance to 15% of control values (from 3.28 +/- 1.40 to 0.49 +/- 0.07 ml/kg/min, p < 0.005), prolonged the elimination half-life (from 0.92 +/- 0.32 to 5.1 +/- 0.9 hours, p < 0.001), and caused a twofold increase in peak plasma chlorzoxazone concentrations (20.6 +/- 9.9 versus 38.7 +/- 10.3 micrograms/ml, p < 0.001). Disulfiram also profoundly decreased the formation clearance of 6-hydroxychlorzoxazone, from 2.30 +/- 0.93 to 0.17 +/- 0.05 ml/kg/min (p < 0.005). These findings show that a single dose of disulfiram significantly diminishes the activity of human P450 2E1 in vivo. The efficacy of single-dose disulfiram as an inhibitor of human P450 2E1 suggests that this modality for manipulating clinical P450 2E1 activity may provide a useful probe for delineating P450 2E1 participation in human drug biotransformation or for the treatment of poisoning by P450 2E1-activated toxins.
8870687
9393675
Pretranslational and posttranslational regulation of rat hepatic CYPs 3A2 and 2E1 by disulfiram.. R Martini; M Ingelman-Sundberg; M Murray (1997) Biochemical pharmacology display abstract
The aldehyde dehydrogenase inhibitor disulfiram (DS) has been used to deter drinking in alcoholics, but it also precipitates pharmacokinetic interactions with coadministered drugs. From previous experiments conducted in vitro, it has been proposed that the ethanol-inducible cytochrome P450 2E1 (CYP2E1) is the major target for inhibition by DS, but the inference from reported drug interactions is that the drug inhibits multiple CYPs. The aim of the present study was to evaluate the inhibition of major constitutive CYPs in rat liver by DS. Thus, the effects of DS on activities mediated by CYPs 2A1/2, 2C11, 2E1, and 3A, which constitute approximately 80% of total CYPs in male rat liver, were evaluated. It was found that CYP2E1-mediated aniline 4-hydroxylase activity was weakly inhibited by DS in vitro, but that preincubation of the drug with NADPH-supplemented microsomes to generate metabolites of DS enhanced the extent of inhibition somewhat. In contrast, constitutive testosterone hydroxylases were inhibited effectively at low concentrations of DS (20 microM decreased the activities of all hydroxylation pathways to 40-60% of control), and a preincubation step between DS and NADPH-fortified microsomes enhanced the inhibition of CYP2C11 and 3A2 activities. In vivo studies were undertaken in which a single dose of DS (100 mg/kg, i.p.) was administered to rats; 24 hr later, CYP2E1-mediated aniline 4-hydroxylase activity was decreased to about 50% of the activity in untreated control rats. CYP2E1 apoprotein and mRNA were also decreased to 38% of the respective control, and CYP3A apoprotein and CYP3A2 mRNA responded similarly. In contrast, CYP2C11 apoprotein was decreased to 66% of control after DS administration, and CYP2A1 expression was unchanged. These findings establish that multiple CYPs are targets for inhibition by DS and provide a basis for clinically significant drug interactions involving CYPs other than 2E1. In addition, the in vivo modulation of CYP function by DS administration is not restricted to enzyme inactivation and may also include down-regulatory effects mediated at a pretranslational level.
SuperCyp