Disulfiram (T3D2557)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (24)XML
Targets (24)
Record Information
Version2.0
Creation Date2009-07-05 02:56:35 UTC
Update Date2014-12-24 20:25:42 UTC
Accession NumberT3D2557
Identification
Common NameDisulfiram
ClassSmall Molecule
DescriptionA 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. [PubChem]
Compound Type
  • Alcohol Deterrent
  • Amine
  • Drug
  • Enzyme Inhibitor
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
1,1'-dithiobis(N,N-diethylthioformamide)
Antabus
Antabuse
Antaethyl
Antalcol
Anticol
Antietanol
Bis(diethylthiocarbamoyl) disulfide
Chronol
Disulfuram
Disulphuram
Dupon 4472
Dupont Fungicide 4472
Esperal
N,N,N',N'-tetraethylthiuram disulfide
TATD
TETD
Tetraethylthioperoxydicarbonic Diamide
Tetraethylthiram Disulfide
Tetraethylthiram Disulphide
Tetraethylthiuram
Tetraethylthiuram Disulfide
Tetraethylthiuram Disulphide
Tetraethylthiuram Sulfide
Tetraethylthiuran Disulfide
TTD
Usaf B-33
Chemical FormulaC10H20N2S4
Average Molecular Mass296.539 g/mol
Monoisotopic Mass296.051 g/mol
CAS Registry Number97-77-8
IUPAC NameN,N-diethyl[(diethylcarbamothioyl)disulfanyl]carbothioamide
Traditional Namedisulfiram
SMILESCCN(CC)C(=S)SSC(=S)N(CC)CC
InChI IdentifierInChI=1S/C10H20N2S4/c1-5-11(6-2)9(13)15-16-10(14)12(7-3)8-4/h5-8H2,1-4H3
InChI KeyInChIKey=AUZONCFQVSMFAP-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as thiuram disulfides. These are organic disulfides that have the general structural formula RN(R')C(=S)SSC(=S)N(R\")R\"', where R-R\"'=alkyl groups.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassAmines
Direct ParentThiuram disulfides
Alternative Parents
Substituents
  • Thiuram disulfide
  • Organic disulfide
  • Sulfenyl compound
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Organosulfur compound
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Disulfiram PathwayNot AvailableNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point71.5°C
Boiling Point117°C at 1.70E+01 mm Hg
Solubility4.09 mg/L (at 25°C)
LogP3.88
Predicted Properties
PropertyValueSource
Water Solubility0.013 g/LALOGPS
logP3.88ALOGPS
logP4.16ChemAxon
logS-4.4ALOGPS
Physiological Charge0ChemAxon
Hydrogen Acceptor Count0ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity88.24 m³·mol⁻¹ChemAxon
Polarizability31.6 ųChemAxon
Number of Rings0ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-016r-8930000000-ff4b800eacdb52d66d802017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-014i-0900000000-274003127d4c34f9abcc2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-002b-1910000000-0371815b89a4378bec812017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004i-0950000000-ca28d8dfdf780c2017162017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004i-0950000000-ca28d8dfdf780c2017162017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0a4i-5910000000-7dd7b7fbb29b6ae08f4c2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00xr-0904000000-2d29367629d096da47082017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00xr-1914000000-0022574151f222c8050f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-014j-0900000000-07fd862cac7fb47fa0072017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0903000000-bb7b2b338b8981b249ac2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00kb-3910100000-263484085094fbdd45da2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-014s-5900000000-fe9f3fb3c9d4c94f64962021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-1970000000-87dad5bd832c248e4c732016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-3900000000-f7637bebace8002bdd782016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00di-9500000000-491cc5b9b0d4455ff6742016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-01vk-4690000000-64528d1f9696aa7a5d5d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-02ft-9810000000-825b92854771a0e58c9d2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0fdo-8910000000-afd3a638d74e8761c5182016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0910000000-cf16eb2676d288479eac2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014i-2900000000-2765ff0428d56cf810492021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-9200000000-7f8c0eb726cf3929fa7f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-3690000000-f14241348cdf9f8196d22021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01ot-7900000000-1843982004d8ffd33a5f2021-10-11View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03di-9200000000-28f4b4954161ce60f7332021-10-11View Spectrum
MSMass Spectrum (Electron Ionization)splash10-014r-9510000000-2e18f478f9c0f9a2958a2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 90 MHz, CDCl3, experimental)Not Available2014-09-20View Spectrum
1D NMR13C NMR Spectrum (1D, 25.16 MHz, CDCl3, experimental)Not Available2014-09-23View Spectrum
Toxicity Profile
Route of ExposureInhalation (MSDS, A308); ingestion (MSDS, A308); dermal (MSDS, A308) ; eye contact (MSDS, A308) Disulfiram is absorbed slowly from the gastrointestinal tract (80 to 90% of oral dose).
Mechanism of ToxicityDisulfiram blocks the oxidation of alcohol at the acetaldehyde stage during alcohol metabolism following disulfiram intake causing an accumulation of acetaldehyde in the blood producing highly unpleasant symptoms. Disulfiram blocks the oxidation of alcohol through its irreversible inactivation of aldehyde dehydrogenase, which acts in the second step of ethanol utilization. In addition, disulfiram competitively binds and inhibits the peripheral benzodiazepine receptor, which may indicate some value in the treatment of the symptoms of alcohol withdrawal, however this activity has not been extensively studied.
MetabolismDisulfiram is completely absorbed from the human GI tract. However, a period of 12 hr is required for its full action, perhaps because, being highly sol in lipid, it is initially localized in fat. It is slowly metabolized in the liver to diethyldithiocarbamate, diethylamine, and carbon disulfide. Six hr after oral administration of the drug, one third of plasma disulfiram is in the form of diethyldithiocarbamate. Elimination is relatively slow, and about 1/5 still remains in body at end of a week. The greater part of the absorbed drug is excreted in the urine as the sulfate, partly free and partly esterified (4, 5).
Toxicity ValuesLD50: 8.6g/kg (oral, rat).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (10)
Uses/SourcesFor the treatment and management of chronic alcoholism (1).
Minimum Risk LevelNot Available
Health EffectsOccasionally implicated in producing psychosis, optic neuritis, and encephalopathy. Hematologic, neuromuscular, and gastrointestinal toxicity and hepatotoxicity may occur 10 days to 12 months after therapy is begun (7).
SymptomsSymptoms of overdose include irritation, slight drowsiness, unpleasant taste, mild GI disturbances, and orthostatic hypotension.
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00822
HMDB IDHMDB14960
PubChem Compound ID3117
ChEMBL IDCHEMBL964
ChemSpider ID3005
KEGG IDC01692
UniProt IDNot Available
OMIM ID
ChEBI ID4659
BioCyc IDDISULFIRAM
CTD IDD004221
Stitch IDDisulfiram
PDB IDNot Available
ACToR ID1353
Wikipedia LinkDisulfiram
References
Synthesis Reference

Adams, H.S. and Meuser, L.; US.Patent 1,782,111; November 18,1930; assigned to The
Naugatuck Chemical Company.
Bailey, G.C.; U.S.Patent 1,796,977; March 17,1931; assigned to The Roessler & Hasslacher
Chemical Company.

MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Nash T, Rice WG: Efficacies of zinc-finger-active drugs against Giardia lamblia. Antimicrob Agents Chemother. 1998 Jun;42(6):1488-92. [9624499 ]
  3. Bouma MJ, Snowdon D, Fairlamb AH, Ackers JP: Activity of disulfiram (bis(diethylthiocarbamoyl)disulphide) and ditiocarb (diethyldithiocarbamate) against metronidazole-sensitive and -resistant Trichomonas vaginalis and Tritrichomonas foetus. J Antimicrob Chemother. 1998 Dec;42(6):817-20. [10052908 ]
  4. Segura-Aguilar J: Peroxidase activity of liver microsomal vitamin D 25-hydroxylase and cytochrome P450 1A2 catalyzes 25-hydroxylation of vitamin D3 and oxidation of dopamine to aminochrome. Biochem Mol Med. 1996 Jun;58(1):122-9. [8809353 ]
  5. David DJ, Bourin M, Hascoet M, Colombel MC, Baker GB, Jolliet P: Comparison of antidepressant activity in 4- and 40-week-old male mice in the forced swimming test: involvement of 5-HT1A and 5-HT1B receptors in old mice. Psychopharmacology (Berl). 2001 Feb;153(4):443-9. [11243491 ]
  6. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. doi: 10.1124/mi.9.4.6. [19720750 ]
  7. Rumack BH (2009). POISINDEX(R) Information System. Englewood, CO: Micromedex, Inc. CCIS Volume 141, edition expires Aug, 2009.
  8. McEvoy GK (ed) (2005). American Hospital Formulary Service - Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacists, Inc.
  9. Clayton GD and Clayton FE (eds) (1981-1982). Patty's Industrial Hygiene and Toxicology: Volume 2A, 2B, 2C: Toxicology. 3rd ed. New York: John Wiley Sons.
  10. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
  11. Drugs.com [Link]
  12. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

Target Details
1. Translocator protein
General Function:
Cholesterol binding
Specific Function:
Can bind protoporphyrin IX and may play a role in the transport of porphyrins and heme (By similarity). Promotes the transport of cholesterol across mitochondrial membranes and may play a role in lipid metabolism (PubMed:24814875), but its precise physiological role is controversial. It is apparently not required for steroid hormone biosynthesis. Was initially identified as peripheral-type benzodiazepine receptor; can also bind isoquinoline carboxamides (PubMed:1847678).
Gene Name:
TSPO
Uniprot ID:
P30536
Molecular Weight:
18827.81 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.28 uMNVS_MP_hPBRNovascreen
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]
  3. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
2. Aldehyde dehydrogenase, mitochondrial
General Function:
Electron carrier activity
Specific Function:
Not Available
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular Weight:
56380.93 Da
References
  1. Mackenzie IS, Maki-Petaja KM, McEniery CM, Bao YP, Wallace SM, Cheriyan J, Monteith S, Brown MJ, Wilkinson IB: Aldehyde dehydrogenase 2 plays a role in the bioactivation of nitroglycerin in humans. Arterioscler Thromb Vasc Biol. 2005 Sep;25(9):1891-5. Epub 2005 Jul 28. [16051882 ]
  2. Ho MP, Yo CH, Liu CM, Chen CL, Lee CC: Refractive hypotension in a patient with disulfiram-ethanol reaction. Am J Med Sci. 2007 Jan;333(1):53-5. [17220694 ]
Target Details
3. Aldehyde dehydrogenase X, mitochondrial
General Function:
Aldehyde dehydrogenase (nad) activity
Specific Function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation.
Gene Name:
ALDH1B1
Uniprot ID:
P30837
Molecular Weight:
57205.93 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
4. Aldehyde dehydrogenase family 1 member A3
General Function:
Thyroid hormone binding
Specific Function:
Recognizes as substrates free retinal and cellular retinol-binding protein-bound retinal. Seems to be the key enzyme in the formation of an RA gradient along the dorso-ventral axis during the early eye development and also in the development of the olfactory system (By similarity).
Gene Name:
ALDH1A3
Uniprot ID:
P47895
Molecular Weight:
56107.995 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
5. Aldehyde dehydrogenase family 16 member A1
General Function:
Aldehyde dehydrogenase (nad) activity
Specific Function:
Not Available
Gene Name:
ALDH16A1
Uniprot ID:
Q8IZ83
Molecular Weight:
85126.605 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
6. Aldehyde dehydrogenase family 3 member B1
General Function:
Aldehyde dehydrogenase [nad(p)+] activity
Specific Function:
Oxidizes medium and long chain saturated and unsaturated aldehydes. Metabolizes also benzaldehyde. Low activity towards acetaldehyde and 3,4-dihydroxyphenylacetaldehyde. May not metabolize short chain aldehydes. May use both NADP(+) and NAD(+) as cofactors. May have a protective role against the cytotoxicity induced by lipid peroxidation.
Gene Name:
ALDH3B1
Uniprot ID:
P43353
Molecular Weight:
51839.245 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
7. Aldehyde dehydrogenase family 3 member B2
General Function:
Aldehyde dehydrogenase [nad(p)+] activity
Specific Function:
Not Available
Gene Name:
ALDH3B2
Uniprot ID:
P48448
Molecular Weight:
42634.6 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
8. Aldehyde dehydrogenase family 8 member A1
General Function:
Retinal dehydrogenase activity
Specific Function:
Converts 9-cis-retinal to 9-cis-retinoic acid. Has lower activity towards 13-cis-retinal. Has much lower activity towards all-trans-retinal. Has highest activity with benzaldehyde and decanal (in vitro). Has a preference for NAD, but shows considerable activity with NADP (in vitro).
Gene Name:
ALDH8A1
Uniprot ID:
Q9H2A2
Molecular Weight:
53400.88 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
9. Aldehyde dehydrogenase, dimeric NADP-preferring
General Function:
Benzaldehyde dehydrogenase (nad+) activity
Specific Function:
ALDHs play a major role in the detoxification of alcohol-derived acetaldehyde. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. This protein preferentially oxidizes aromatic aldehyde substrates. It may play a role in the oxidation of toxic aldehydes.
Gene Name:
ALDH3A1
Uniprot ID:
P30838
Molecular Weight:
50394.57 Da
References
  1. Wikipedia. Disulfiram. Last Updated 14 June 2009. [Link]
Target Details
10. Apelin receptor
General Function:
Receptor activity
Specific Function:
Receptor for apelin coupled to G proteins that inhibit adenylate cyclase activity and plays a role in various processes in adults such as regulation of blood pressure, heart contractility, and heart failure. Also plays a key role in early development such as gastrulation and heart morphogenesis by acting as a receptor for APELA hormone. Alternative coreceptor with CD4 for HIV-1 infection; may be involved in the development of AIDS dementia.
Gene Name:
APLNR
Uniprot ID:
P35414
Molecular Weight:
42660.055 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC502.63 uMNot AvailableBindingDB 50058655
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
11. Dopamine beta-hydroxylase
General Function:
L-ascorbic acid binding
Specific Function:
Conversion of dopamine to noradrenaline.
Gene Name:
DBH
Uniprot ID:
P09172
Molecular Weight:
69064.45 Da
References
  1. Gaval-Cruz M, Weinshenker D: mechanisms of disulfiram-induced cocaine abstinence: antabuse and cocaine relapse. Mol Interv. 2009 Aug;9(4):175-87. doi: 10.1124/mi.9.4.6. [19720750 ]
Target Details
12. Fatty-acid amide hydrolase 1
General Function:
Fatty acid amide hydrolase activity
Specific Function:
Degrades bioactive fatty acid amides like oleamide, the endogenous cannabinoid, anandamide and myristic amide to their corresponding acids, thereby serving to terminate the signaling functions of these molecules. Hydrolyzes polyunsaturated substrate anandamide preferentially as compared to monounsaturated substrates.
Gene Name:
FAAH
Uniprot ID:
O00519
Molecular Weight:
63065.28 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50363.07805 uMNot AvailableBindingDB 50058655
References
  1. Kapanda CN, Muccioli GG, Labar G, Poupaert JH, Lambert DM: Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors. J Med Chem. 2009 Nov 26;52(22):7310-4. doi: 10.1021/jm901323s. [19883085 ]
Target Details
13. Monoglyceride lipase
General Function:
Protein homodimerization activity
Specific Function:
Converts monoacylglycerides to free fatty acids and glycerol. Hydrolyzes the endocannabinoid 2-arachidonoylglycerol, and thereby contributes to the regulation of endocannabinoid signaling, nociperception and perception of pain (By similarity). Regulates the levels of fatty acids that serve as signaling molecules and promote cancer cell migration, invasion and tumor growth (PubMed:20079333).
Gene Name:
MGLL
Uniprot ID:
Q99685
Molecular Weight:
33261.13 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.25893 uMNot AvailableBindingDB 50058655
References
  1. Kapanda CN, Muccioli GG, Labar G, Poupaert JH, Lambert DM: Bis(dialkylaminethiocarbonyl)disulfides as potent and selective monoglyceride lipase inhibitors. J Med Chem. 2009 Nov 26;52(22):7310-4. doi: 10.1021/jm901323s. [19883085 ]
Target Details
14. Perilipin-1
General Function:
Lipid binding
Specific Function:
Modulator of adipocyte lipid metabolism. Coats lipid storage droplets to protect them from breakdown by hormone-sensitive lipase (HSL). Its absence may result in leanness. Plays a role in unilocular lipid droplet formation by activating CIDEC. Their interaction promotes lipid droplet enlargement and directional net neutral lipid transfer. May modulate lipolysis and triglyceride levels.
Gene Name:
PLIN1
Uniprot ID:
O60240
Molecular Weight:
55989.785 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC506.959 uMNot AvailableBindingDB 50058655
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
15. Perilipin-5
General Function:
Not Available
Specific Function:
Lipid droplet-associated protein that maintains the balance between lipogenesis and lipolysis and also regulates fatty acid oxidation in oxidative tissues. Recruits mitochondria to the surface of lipid droplets and is involved in lipid droplet homeostasis by regulating both the storage of fatty acids in the form of triglycerides and the release of fatty acids for mitochondrial fatty acid oxidation. In lipid droplet triacylglycerol hydrolysis, plays a role as a scaffolding protein for three major key lipolytic players: ABHD5, PNPLA2 and LIPE. Reduces the triacylglycerol hydrolase activity of PNPLA2 by recruiting and sequestering PNPLA2 to lipid droplets. Phosphorylation by PKA enables lipolysis probably by promoting release of ABHD5 from the perilipin scaffold and by facilitating interaction of ABHD5 with PNPLA2. Also increases lipolysis through interaction with LIPE and upon PKA-mediated phosphorylation of LIPE (By similarity).
Gene Name:
PLIN5
Uniprot ID:
Q00G26
Molecular Weight:
50790.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.622 uMNot AvailableBindingDB 50058655
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
16. Type-1 angiotensin II receptor
General Function:
Protein heterodimerization activity
Specific Function:
Receptor for angiotensin II. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.
Gene Name:
AGTR1
Uniprot ID:
P30556
Molecular Weight:
41060.53 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC506.637 uMNot AvailableBindingDB 50058655
References
  1. Liu T, Lin Y, Wen X, Jorissen RN, Gilson MK: BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities. Nucleic Acids Res. 2007 Jan;35(Database issue):D198-201. Epub 2006 Dec 1. [17145705 ]
Target Details
17. Peroxisome proliferator-activated receptor gamma
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated proinflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of ARNTL/BMAL1 in the blood vessels (By similarity).
Gene Name:
PPARG
Uniprot ID:
P37231
Molecular Weight:
57619.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.20 uMTox21_PPARg_BLA_Agonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
18. Cellular tumor antigen p53
General Function:
Not Available
Specific Function:
Not Available
Gene Name:
TP53
Uniprot ID:
P04637
Molecular Weight:
43652.79 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.39 uMAPR_p53Act_72h_upApredica
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
19. Cytochrome P450 2C19
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.93 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
20. Substance-K receptor
General Function:
Tachykinin receptor activity
Specific Function:
This is a receptor for the tachykinin neuropeptide substance K (neurokinin A). It is associated with G proteins that activate a phosphatidylinositol-calcium second messenger system. The rank order of affinity of this receptor to tachykinins is: substance K > neuromedin-K > substance P.
Gene Name:
TACR2
Uniprot ID:
P21452
Molecular Weight:
44441.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.39 uMNVS_GPCR_hNK2Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
21. Cytochrome P450 2C9
General Function:
Steroid hydroxylase activity
Specific Function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular Weight:
55627.365 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.79 uMNVS_ADME_hCYP2C9Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
22. D(1A) dopamine receptor
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.79 uMNVS_GPCR_hDRD1Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
23. 5-hydroxytryptamine receptor 6
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase. It has a high affinity for tricyclic psychotropic drugs (By similarity). Controls pyramidal neurons migration during corticogenesis, through the regulation of CDK5 activity (By similarity). Is an activator of TOR signaling (PubMed:23027611).
Gene Name:
HTR6
Uniprot ID:
P50406
Molecular Weight:
46953.625 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC508.87 uMNVS_GPCR_h5HT6Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
Target Details
24. 5-hydroxytryptamine receptor 7
General Function:
Serotonin receptor activity
Specific Function:
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
Molecular Weight:
53554.43 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC5010.00 uMNVS_GPCR_h5HT7Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]