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Record Information
Version2.0
Creation Date2009-07-05 03:35:09 UTC
Update Date2014-12-24 20:25:43 UTC
Accession NumberT3D2576
Identification
Common NameHaloperidol
ClassSmall Molecule
DescriptionA phenyl-piperidinyl-butyrophenone that is used primarily to treat schizophrenia and other psychoses. It is also used in schizoaffective disorder, delusional disorders, ballism, and tourette syndrome (a drug of choice) and occasionally as adjunctive therapy in mental retardation and the chorea of huntington disease. It is a potent antiemetic and is used in the treatment of intractable hiccups. (From AMA Drug Evaluations Annual, 1994, p279)
Compound Type
  • Amine
  • Antidyskinetic
  • Antiemetic
  • Antipsychotic Agent
  • Butyrophenone
  • Dopamine Antagonist
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Organochloride
  • Organofluoride
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
1-(3-P-Fluorobenzoylpropyl)-4-P-chlorophenyl-4-hydroxypiperidine
4'-Fluoro-4-(4-(P-chlorophenyl)-4-hydroxypiperidinyl)butyrophenone
4'-Fluoro-4-(4-hydroxy-4-(4'-chlorophenyl)piperidino)butyrophenone
4-(4-(Para-chlorophenyl)-4-hydroxypiperidino)-4'-fluorobutyrophenone
4-[4-(4-Chlorophenyl)-4-hydroxy-1-piperidyl]-1-(4-fluorophenyl)-butan-1-one
Aloperidin
Bioperidolo
Brotopon
Dozic
Duraperidol
Einalon S
Eukystol
gamma-(4-(P-Chlorophenyl)-4-hydroxpiperidino)-P-fluorbutyrophenone
Haldol
Haloperidolum
Halosten
Keselan
Linton
Peluces
Serenace
Sigaperidol
Chemical FormulaC21H23ClFNO2
Average Molecular Mass375.864 g/mol
Monoisotopic Mass375.140 g/mol
CAS Registry Number52-86-8
IUPAC Name4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]-1-(4-fluorophenyl)butan-1-one
Traditional Namehaloperidol
SMILESOC1(CCN(CCCC(=O)C2=CC=C(F)C=C2)CC1)C1=CC=C(Cl)C=C1
InChI IdentifierInChI=1S/C21H23ClFNO2/c22-18-7-5-17(6-8-18)21(26)11-14-24(15-12-21)13-1-2-20(25)16-3-9-19(23)10-4-16/h3-10,26H,1-2,11-15H2
InChI KeyInChIKey=LNEPOXFFQSENCJ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as alkyl-phenylketones. These are aromatic compounds containing a ketone substituted by one alkyl group, and a phenyl group.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAlkyl-phenylketones
Alternative Parents
Substituents
  • Alkyl-phenylketone
  • Phenylpiperidine
  • Butyrophenone
  • Phenylbutylamine
  • Benzoyl
  • Aryl alkyl ketone
  • Aralkylamine
  • Chlorobenzene
  • Fluorobenzene
  • Halobenzene
  • Aryl chloride
  • Aryl fluoride
  • Aryl halide
  • Monocyclic benzene moiety
  • Gamma-aminoketone
  • Benzenoid
  • Piperidine
  • Tertiary alcohol
  • Tertiary amine
  • Tertiary aliphatic amine
  • Azacycle
  • Organoheterocyclic compound
  • Organofluoride
  • Organochloride
  • Organohalogen compound
  • Amine
  • Organic nitrogen compound
  • Alcohol
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite to faintly yellowish, amorphous or micro-crystalline powder (2).
Experimental Properties
PropertyValue
Melting Point151.5°C
Boiling PointNot Available
Solubility14 mg/L (at 25°C)
LogP4.3
Predicted Properties
PropertyValueSource
Water Solubility0.0045 g/LALOGPS
logP3.7ALOGPS
logP3.66ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)13.96ChemAxon
pKa (Strongest Basic)8.05ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity102.59 m³·mol⁻¹ChemAxon
Polarizability39.15 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00di-3941000000-d115a40817bca84c859aJSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-5941100000-c3840be760880e2d998aJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004i-0009000000-cdfdd91dd85d2c1cbd3dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00or-0409000000-d542c35143556b83b87aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0900000000-3985dded029c89448ebeJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-01b9-0900000000-720c0a4f1130b4237f32JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-00di-0900000000-772a799ebb3b949cef0cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-004i-0009000000-21c8918254235e561129JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-014i-0904000000-8c97cb39f9680dd91378JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-01b9-0900000000-571a03ebb5faa3e5cd63JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00di-0900000000-62e233fd691121c78e96JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00di-0900000000-91bf80d34ef94ed709f0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00di-0900000000-46ef29917220709863a4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00di-3900000000-26f391756d439f7dbfc8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00b9-9600000000-404fc399b40cfb560a99JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-00b9-9100000000-8779758823471091566aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-1619000000-27aa28ad7f91429f5ae7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-004i-0609000000-f7c623630d33dbd89e2bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-01b9-3911000000-78d5b34044714e81aec3JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a6r-0009000000-abe4b4cad1298a753614JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a6r-0679000000-5910dd3a7977bc423000JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00l6-4961000000-075c4f60c9298ff5cd1eJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0009000000-c5a2526394d0eaf36160JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-1329000000-8e1f1a55517bf6e11ca4JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-03dj-3920000000-2f2c54905c928d8238fbJSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0079-3290000000-cc6a990404ba7b9452a8JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureInhalation, Oral (60%)
Mechanism of ToxicityThe precise mechanism whereby the therapeutic effects of haloperidol are produced is not known, but the drug appears to depress the CNS at the subcortical level of the brain, midbrain, and brain stem reticular formation. Haloperidol seems to inhibit the ascending reticular activating system of the brain stem (possibly through the caudate nucleus), thereby interrupting the impulse between the diencephalon and the cortex. The drug may antagonize the actions of glutamic acid within the extrapyramidal system, and inhibitions of catecholamine receptors may also contribute to haloperidol's mechanism of action. Haloperidol may also inhibit the reuptake of various neurotransmitters in the midbrain, and appears to have a strong central antidopaminergic and weak central anticholinergic activity. The drug produces catalepsy and inhibits spontaneous motor activity and conditioned avoidance behaviours in animals. The exact mechanism of antiemetic action of haloperidol has also not been fully determined, but the drug has been shown to directly affect the chemoreceptor trigger zone (CTZ) through the blocking of dopamine receptors in the CTZ.
MetabolismHaloperidol is well absorbed from the gastrointestinal tract but first-pass hepatic metabolism decreases oral bioavailability to 40 to 75%. Serum concentration peaks 0.5 to 4 hours after an oral dose. Following administration of haloperidol, the drug is distributed mainly into the liver, with lower concentrations being distributed into the brain, lung, kidneys, spleen, and heart. Although the exact metabolic fate has not been clearly established, it appears that haloperidol is principally metabolized in the liver. The drug appears to be metabolized principally by oxidative N-dealkylation of the piperidine nitrogen to form fluorophenylcarbonic acids and piperidine metabolites (which appear to be inactive), and by reduction of the butyrophenone carbonyl to the carbinol, forming hydroxyhaloperidol. Limited data suggest that the reduced metabolite, hydroxyhaloperidol, has some pharmacologic activity, although its activity appears to be less than that of haloperidol. Urinary metabolites include p-fluorophenaceturic acid, beta-p-fluorobenzoylpropionic acid, and several unidentified acids (3, 4, 3). Half Life: 3 weeks
Toxicity ValuesLD50: 128 mg/kg (Oral, Rat) LD50: 71 mg/kg (Oral, Mouse) LD50: 90 mg/kg (Oral, Dog) LD50: 165 mg/kg (Oral, Rat)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor the management of psychotic disorders (eg. schizophrenia) and delirium, as well as to control tics and vocal utterances of Tourette's syndrome (Gilles de la Tourette's syndrome). Also used for the treatment of severe behavioural problems in children with disrubtive behaviour disorder or ADHD (attention-deficit hyperactivity disorder). Haloperidol has been used in the prevention and control of severe nausea and vomiting.
Minimum Risk LevelNot Available
Health EffectsTachycardia, hypotension, and hypertension; Extrapyramidal Symptoms (EPS) such as akathisia, or dystonia; impaired liver function and/or jaundice have been reported. Maculopapular and acneiform skin reactions and isolated cases of photosensitivity and loss of hair.Laryngospasm, bronchospasm, cataracts, retinopathy and visual disturbances; lactation, breast engorgement, mastalgia, menstrual irregularities, gynecomastia, impotence, increased libido, hyperglycemia, hypoglycemia and hyponatremia (RxList, A308).
SymptomsLD50=165 mg/kg (rats, oral)
TreatmentSince there is no specific antidote, treatment is primarily supportive. A patent airway must be established by use of an oropharyngeal airway or endotracheal tube or, in prolonged cases of coma, by tracheostomy. Respiratory depression may be counteracted by artificial respiration and mechanical respirators. Hypotension and circulatory collapse may be counteracted by use of intravenous fluids, plasma, or concentrated albumin, and vasopressor agents such as metaraminol, phenylephrine and norepinephrine. Epinephrine should not be used. In case of severe extrapyramidal reactions, anti-Parkinson medication should be administered. ECG and vital signs should be monitored especially for signs of Q-T prolongation or dysrhythmias and monitoring should continue until the ECG is normal. Severe arrhythmias should be treated with appropriate anti-arrhythmic measures. (11)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00502
HMDB IDHMDB14645
PubChem Compound ID3559
ChEMBL IDCHEMBL54
ChemSpider ID3438
KEGG IDC01814
UniProt IDNot Available
OMIM ID
ChEBI ID5613
BioCyc IDNot Available
CTD IDNot Available
Stitch IDHaloperidol
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkHaloperidol
References
Synthesis Reference

DrugSyn.org

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. Sax KW, Strakowski SM: Behavioral sensitization in humans. J Addict Dis. 2001;20(3):55-65. [11681593 ]
  3. Chaudhry IA, Turkanis SA, Karler R: Characteristics of "reverse tolerance" to amphetamine-induced locomotor stimulation in mice. Neuropharmacology. 1988 Aug;27(8):777-81. [3216957 ]
  4. Zhang M, Hu P, Krois CR, Kane MA, Napoli JL: Altered vitamin A homeostasis and increased size and adiposity in the rdh1-null mouse. FASEB J. 2007 Sep;21(11):2886-96. Epub 2007 Apr 13. [17435174 ]
  5. Niemegeers CJ, Laduron PM: Pharmacology and biochemistry of haloperidol. Proc R Soc Med. 1976;69 suppl 1:3-8. [14331 ]
  6. Ellenhorn MJ, Schonwald S, Ordog G, Wasserberger J (1997). Ellenhorn's Medical Toxicology: Diagnosis and Treatment of Human Poisoning. 2nd ed. Baltimore, MD: Williams and Wilkins.
  7. Barnhart ER (1988). Physicians' Desk Reference. 42 ed. Oradell, NJ: Medical Economics Co. Inc.
  8. McEvoy GK (ed) (2003). American Hospital Formulary Service - Drug Information 2003. Bethesda, MD: American Society of Health-System Pharmacists, Inc.
  9. McEvoy GK (ed) (1990). American Hospital Formulary Service - Drug Information 1990. Bethesda, MD: American Society of Health-System Pharmacists, Inc.
  10. Drugs.com [Link]
  11. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.0013 uMNot AvailableBindingDB 21398
IC500.005 uMNot AvailableBindingDB 21398
IC500.006 uMNot AvailableBindingDB 21398
IC500.0065 uMNot AvailableBindingDB 21398
AC500.01 uMNVS_GPCR_hDRD4.4Novascreen
References
  1. Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V: N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide: a potent and selective dopamine D4 ligand. J Med Chem. 1998 Nov 19;41(24):4903-9. [9822559 ]
  2. Zhang X, Hodgetts K, Rachwal S, Zhao H, Wasley JW, Craven K, Brodbeck R, Kieltyka A, Hoffman D, Bacolod MD, Girard B, Tran J, Thurkauf A: trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents. J Med Chem. 2000 Oct 19;43(21):3923-32. [11052797 ]
  3. Hrib NJ, Jurcak JG, Bregna DE, Burgher KL, Hartman HB, Kafka S, Kerman LL, Kongsamut S, Roehr JE, Szewczak MR, Woods-Kettelberger AT, Corbett R: Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate. J Med Chem. 1996 Sep 27;39(20):4044-57. [8831770 ]
  4. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
  5. 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 ]
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.004 uMNot AvailableBindingDB 21398
IC500.0041 uMNot AvailableBindingDB 21398
IC500.0049 uMNot AvailableBindingDB 21398
IC500.55 uMNot AvailableBindingDB 21398
AC500.02 uMNVS_GPCR_hDRD2sNovascreen
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Osinski MA, Uchic ME, Seifert T, Shaughnessy TK, Miller LN, Nakane M, Cox BF, Brioni JD, Moreland RB: Dopamine D2, but not D4, receptor agonists are emetogenic in ferrets. Pharmacol Biochem Behav. 2005 May;81(1):211-9. [15894081 ]
  3. Bustillo J, Barrow R, Paz R, Tang J, Seraji-Bozorgzad N, Moore GJ, Bolognani F, Lauriello J, Perrone-Bizzozero N, Galloway MP: Long-term treatment of rats with haloperidol: lack of an effect on brain N-acetyl aspartate levels. Neuropsychopharmacology. 2006 Apr;31(4):751-6. [16132064 ]
  4. Ishiwata K, Oda K, Sakata M, Kimura Y, Kawamura K, Oda K, Sasaki T, Naganawa M, Chihara K, Okubo Y, Ishii K: A feasibility study of [11C]SA4503-PET for evaluating sigmal receptor occupancy by neuroleptics: the binding of haloperidol to sigma1 and dopamine D2-like receptors. Ann Nucl Med. 2006 Oct;20(8):569-73. [17134027 ]
  5. Zhang X, Hodgetts K, Rachwal S, Zhao H, Wasley JW, Craven K, Brodbeck R, Kieltyka A, Hoffman D, Bacolod MD, Girard B, Tran J, Thurkauf A: trans-1-[(2-Phenylcyclopropyl)methyl]-4-arylpiperazines: mixed dopamine D(2)/D(4) receptor antagonists as potential antipsychotic agents. J Med Chem. 2000 Oct 19;43(21):3923-32. [11052797 ]
  6. Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V: N-[2-[4-(4-Chlorophenyl)piperazin-1-yl]ethyl]-3-methoxybenzamide: a potent and selective dopamine D4 ligand. J Med Chem. 1998 Nov 19;41(24):4903-9. [9822559 ]
  7. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
  8. Sun H, Zhu L, Yang H, Qian W, Guo L, Zhou S, Gao B, Li Z, Zhou Y, Jiang H, Chen K, Zhen X, Liu H: Asymmetric total synthesis and identification of tetrahydroprotoberberine derivatives as new antipsychotic agents possessing a dopamine D(1), D(2) and serotonin 5-HT(1A) multi-action profile. Bioorg Med Chem. 2013 Feb 15;21(4):856-68. doi: 10.1016/j.bmc.2012.12.016. Epub 2012 Dec 21. [23332346 ]
  9. Kapur S, McClelland RA, VanderSpek SC, Wadenberg ML, Baker G, Nobrega J, Zipursky RB, Seeman P: Increasing D2 affinity results in the loss of clozapine's atypical antipsychotic action. Neuroreport. 2002 May 7;13(6):831-5. [11997696 ]
  10. Arakawa R, Okumura M, Ito H, Takano A, Takahashi H, Takano H, Maeda J, Okubo Y, Suhara T: Positron emission tomography measurement of dopamine D(2) receptor occupancy in the pituitary and cerebral cortex: relation to antipsychotic-induced hyperprolactinemia. J Clin Psychiatry. 2010 Sep;71(9):1131-7. doi: 10.4088/JCP.08m04307yel. Epub 2010 Feb 23. [20361897 ]
  11. 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 ]
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
AC500.02 uMNVS_GPCR_hDRD1Novascreen
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [16983399 ]
  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 ]
General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.028 uMNot AvailableBindingDB 21398
IC500.0281 uMNot AvailableBindingDB 21398
IC500.03 uMNot AvailableBindingDB 21398
IC500.0302 uMNot AvailableBindingDB 21398
IC500.032 uMNot AvailableBindingDB 21398
IC500.23 uMNot AvailableBindingDB 21398
IC501.1 uMNot AvailableBindingDB 21398
IC501.4 uMNot AvailableBindingDB 21398
References
  1. Rajamani R, Tounge BA, Li J, Reynolds CH: A two-state homology model of the hERG K+ channel: application to ligand binding. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1737-41. [15745831 ]
  2. Cavalli A, Poluzzi E, De Ponti F, Recanatini M: Toward a pharmacophore for drugs inducing the long QT syndrome: insights from a CoMFA study of HERG K(+) channel blockers. J Med Chem. 2002 Aug 29;45(18):3844-53. [12190308 ]
  3. Keseru GM: Prediction of hERG potassium channel affinity by traditional and hologram qSAR methods. Bioorg Med Chem Lett. 2003 Aug 18;13(16):2773-5. [12873512 ]
  4. Tobita M, Nishikawa T, Nagashima R: A discriminant model constructed by the support vector machine method for HERG potassium channel inhibitors. Bioorg Med Chem Lett. 2005 Jun 2;15(11):2886-90. [15911273 ]
  5. Jia L, Sun H: Support vector machines classification of hERG liabilities based on atom types. Bioorg Med Chem. 2008 Jun 1;16(11):6252-60. doi: 10.1016/j.bmc.2008.04.028. Epub 2008 Apr 16. [18448342 ]
  6. Pearlstein RA, Vaz RJ, Kang J, Chen XL, Preobrazhenskaya M, Shchekotikhin AE, Korolev AM, Lysenkova LN, Miroshnikova OV, Hendrix J, Rampe D: Characterization of HERG potassium channel inhibition using CoMSiA 3D QSAR and homology modeling approaches. Bioorg Med Chem Lett. 2003 May 19;13(10):1829-35. [12729675 ]
  7. 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 ]
  8. Sams AG, Larsen K, Mikkelsen GK, Hentzer M, Christoffersen CT, Jensen KG, Frederiksen K, Bang-Andersen B: Hit-to-lead investigation of a series of novel combined dopamine D2 and muscarinic M1 receptor ligands with putative antipsychotic and pro-cognitive potential. Bioorg Med Chem Lett. 2012 Aug 1;22(15):5134-40. doi: 10.1016/j.bmcl.2012.05.048. Epub 2012 May 18. [22677319 ]
  9. Du LP, Tsai KC, Li MY, You QD, Xia L: The pharmacophore hypotheses of I(Kr) potassium channel blockers: novel class III antiarrhythmic agents. Bioorg Med Chem Lett. 2004 Sep 20;14(18):4771-7. [15324906 ]
General Function:
Opioid receptor activity
Specific Function:
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma membrane. Involved in the regulation of different receptors it plays a role in BDNF signaling and EGF signaling. Also regulates ion channels like the potassium channel and could modulate neurotransmitter release. Plays a role in calcium signaling through modulation together with ANK2 of the ITP3R-dependent calcium efflux at the endoplasmic reticulum. Plays a role in several other cell functions including proliferation, survival and death. Originally identified for its ability to bind various psychoactive drugs it is involved in learning processes, memory and mood alteration (PubMed:16472803, PubMed:9341151). Necessary for proper mitochondrial axonal transport in motor neurons, in particular the retrograde movement of mitochondria (By similarity).
Gene Name:
SIGMAR1
Uniprot ID:
Q99720
Molecular Weight:
25127.52 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.0021 uMNot AvailableBindingDB 21398
IC500.004 uMNot AvailableBindingDB 21398
IC500.005 uMNot AvailableBindingDB 21398
IC500.00564 uMNot AvailableBindingDB 21398
IC500.008 uMNot AvailableBindingDB 21398
IC500.017 uMNot AvailableBindingDB 21398
IC500.021 uMNot AvailableBindingDB 21398
IC500.214 uMNot AvailableBindingDB 21398
References
  1. Cazenave Gassiot A, Charton J, Girault-Mizzi S, Gilleron P, Debreu-Fontaine MA, Sergheraert C, Melnyk P: Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 2. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4828-32. [16140009 ]
  2. Charton J, Cazenave Gassiot A, Girault-Mizzi S, Debreu-Fontaine MA, Melnyk P, Sergheraert C: Synthesis and pharmacological evaluation of Tic-hydantoin derivatives as selective sigma1 ligands. Part 1. Bioorg Med Chem Lett. 2005 Nov 1;15(21):4833-7. [16140011 ]
  3. Kimes AS, Wilson AA, Scheffel U, Campbell BG, London ED: Radiosynthesis, cerebral distribution, and binding of [125I]-1-(p-iodophenyl)-3-(1-adamantyl)guanidine, a ligand for sigma binding sites. J Med Chem. 1992 Dec 11;35(25):4683-9. [1469697 ]
  4. Wilson AA, Dannals RF, Ravert HT, Sonders MS, Weber E, Wagner HN Jr: Radiosynthesis of sigma receptor ligands for positron emission tomography: 11C- and 18F-labeled guanidines. J Med Chem. 1991 Jun;34(6):1867-70. [1648140 ]
  5. Perrone R, Berardi F, Colabufo NA, Leopoldo M, Tortorella V, Fiorentini F, Olgiati V, Ghiglieri A, Govoni S: High affinity and selectivity on 5-HT1A receptor of 1-aryl-4-[1-tetralin)alkyl]piperazines. 2. J Med Chem. 1995 Mar 17;38(6):942-9. [7699710 ]
  6. Germain AR, Carmody LC, Nag PP, Morgan B, Verplank L, Fernandez C, Donckele E, Feng Y, Perez JR, Dandapani S, Palmer M, Lander ES, Gupta PB, Schreiber SL, Munoz B: Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells. Bioorg Med Chem Lett. 2013 Mar 15;23(6):1834-8. doi: 10.1016/j.bmcl.2013.01.025. Epub 2013 Jan 16. [23403082 ]
  7. Myers AM, Charifson PS, Owens CE, Kula NS, McPhail AT, Baldessarini RJ, Booth RG, Wyrick SD: Conformational analysis, pharmacophore identification, and comparative molecular field analysis of ligands for the neuromodulatory sigma 3 receptor. J Med Chem. 1994 Nov 25;37(24):4109-17. [7990111 ]
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular Weight:
44224.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.01 uMNot AvailableBindingDB 21398
References
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [7520908 ]
  2. Tuppurainen H, Kuikka JT, Viinamaki H, Husso M, Tiihonen J: Dopamine D2/3 receptor binding potential and occupancy in midbrain and temporal cortex by haloperidol, olanzapine and clozapine. Psychiatry Clin Neurosci. 2009 Aug;63(4):529-37. doi: 10.1111/j.1440-1819.2009.01982.x. Epub 2009 May 22. [19496999 ]
  3. Tadori Y, Forbes RA, McQuade RD, Kikuchi T: Characterization of aripiprazole partial agonist activity at human dopamine D3 receptors. Eur J Pharmacol. 2008 Nov 12;597(1-3):27-33. doi: 10.1016/j.ejphar.2008.09.008. Epub 2008 Sep 20. [18831971 ]
  4. Kessler RM, Ansari MS, Riccardi P, Li R, Jayathilake K, Dawant B, Meltzer HY: Occupancy of striatal and extrastriatal dopamine D2/D3 receptors by olanzapine and haloperidol. Neuropsychopharmacology. 2005 Dec;30(12):2283-9. [16123775 ]
  5. Malmberg, Mikaels, Mohell N: Agonist and inverse agonist activity at the dopamine D3 receptor measured by guanosine 5'--gamma-thio-triphosphate--35S- binding. J Pharmacol Exp Ther. 1998 Apr;285(1):119-26. [9536001 ]
  6. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
General Function:
Zinc ion binding
Specific Function:
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
Gene Name:
GRIN2B
Uniprot ID:
Q13224
Molecular Weight:
166365.885 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Hattori K, Uchino S, Isosaka T, Maekawa M, Iyo M, Sato T, Kohsaka S, Yagi T, Yuasa S: Fyn is required for haloperidol-induced catalepsy in mice. J Biol Chem. 2006 Mar 17;281(11):7129-35. Epub 2006 Jan 10. [16407246 ]
  3. Zhuravliova E, Barbakadze T, Natsvlishvili N, Mikeladze DG: Haloperidol induces neurotoxicity by the NMDA receptor downstream signaling pathway, alternative from glutamate excitotoxicity. Neurochem Int. 2007 Jun;50(7-8):976-82. Epub 2006 Nov 7. [17092607 ]
  4. Gu WH, Yang S, Shi WX, Zhen XC, Jin GZ: Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine. Acta Pharmacol Sin. 2007 Jul;28(7):953-8. [17588330 ]
General Function:
Virus receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates phospholipase C and a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and promotes the release of Ca(2+) ions from intracellular stores. Affects neural activity, perception, cognition and mood. Plays a role in the regulation of behavior, including responses to anxiogenic situations and psychoactive substances. Plays a role in intestinal smooth muscle contraction, and may play a role in arterial vasoconstriction.(Microbial infection) Acts as a receptor for human JC polyomavirus/JCPyV.
Gene Name:
HTR2A
Uniprot ID:
P28223
Molecular Weight:
52602.58 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC500.288 uMNot AvailableBindingDB 21398
References
  1. Leysen JE, Janssen PM, Megens AA, Schotte A: Risperidone: a novel antipsychotic with balanced serotonin-dopamine antagonism, receptor occupancy profile, and pharmacologic activity. J Clin Psychiatry. 1994 May;55 Suppl:5-12. [7520908 ]
  2. Hrib NJ, Jurcak JG, Bregna DE, Burgher KL, Hartman HB, Kafka S, Kerman LL, Kongsamut S, Roehr JE, Szewczak MR, Woods-Kettelberger AT, Corbett R: Structure-activity relationships of a series of novel (piperazinylbutyl)thiazolidinone antipsychotic agents related to 3-[4-[4-(6-fluorobenzo[b]thien-3-yl)-1-piperazinyl]butyl]-2,5,5- trimethyl-4-thiazolidinone maleate. J Med Chem. 1996 Sep 27;39(20):4044-57. [8831770 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM1
Uniprot ID:
P11229
Molecular Weight:
51420.375 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC505.5 uMNot AvailableBindingDB 21398
References
  1. Liao Y, DeBoer P, Meier E, Wikstrom H: Synthesis and pharmacological evaluation of triflate-substituted analogues of clozapine: identification of a novel atypical neuroleptic. J Med Chem. 1997 Dec 5;40(25):4146-53. [9406603 ]
  2. Liao Y, Venhuis BJ, Rodenhuis N, Timmerman W, Wikstrom H, Meier E, Bartoszyk GD, Bottcher H, Seyfried CA, Sundell S: New (sulfonyloxy)piperazinyldibenzazepines as potential atypical antipsychotics: chemistry and pharmacological evaluation. J Med Chem. 1999 Jun 17;42(12):2235-44. [10377229 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling inhibits adenylate cyclase activity and activates a phosphatidylinositol-calcium second messenger system that regulates the release of Ca(2+) ions from intracellular stores. Plays a role in the regulation of 5-hydroxytryptamine release and in the regulation of dopamine and 5-hydroxytryptamine metabolism. Plays a role in the regulation of dopamine and 5-hydroxytryptamine levels in the brain, and thereby affects neural activity, mood and behavior. Plays a role in the response to anxiogenic stimuli.
Gene Name:
HTR1A
Uniprot ID:
P08908
Molecular Weight:
46106.335 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC501.5 uMNot AvailableBindingDB 21398
References
  1. Taverne T, Diouf O, Depreux P, Poupaert JH, Lesieur D, Guardiola-Lemaitre B, Renard P, Rettori MC, Caignard DH, Pfeiffer B: Novel benzothiazolin-2-one and benzoxazin-3-one arylpiperazine derivatives with mixed 5HT1A/D2 affinity as potential atypical antipsychotics. J Med Chem. 1998 Jun 4;41(12):2010-8. [9622542 ]
General Function:
Serotonin receptor activity
Specific Function:
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins and mediate activation of alternative signaling pathways. Signaling activates a phosphatidylinositol-calcium second messenger system that modulates the activity of phosphatidylinositol 3-kinase and down-stream signaling cascades and promotes the release of Ca(2+) ions from intracellular stores. Regulates neuronal activity via the activation of short transient receptor potential calcium channels in the brain, and thereby modulates the activation of pro-opiomelacortin neurons and the release of CRH that then regulates the release of corticosterone. Plays a role in the regulation of appetite and eating behavior, responses to anxiogenic stimuli and stress. Plays a role in insulin sensitivity and glucose homeostasis.
Gene Name:
HTR2C
Uniprot ID:
P28335
Molecular Weight:
51820.705 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>10 uMNot AvailableBindingDB 21398
References
  1. Taverne T, Diouf O, Depreux P, Poupaert JH, Lesieur D, Guardiola-Lemaitre B, Renard P, Rettori MC, Caignard DH, Pfeiffer B: Novel benzothiazolin-2-one and benzoxazin-3-one arylpiperazine derivatives with mixed 5HT1A/D2 affinity as potential atypical antipsychotics. J Med Chem. 1998 Jun 4;41(12):2010-8. [9622542 ]
General Function:
Neuropeptide receptor activity
Specific Function:
Receptor for melanin-concentrating hormone, coupled to both G proteins that inhibit adenylyl cyclase and G proteins that activate phosphoinositide hydrolysis.
Gene Name:
MCHR1
Uniprot ID:
Q99705
Molecular Weight:
45962.185 Da
References
  1. Theisen FM, Haberhausen M, Firnges MA, Gregory P, Reinders JH, Remschmidt H, Hebebrand J, Antel J: No evidence for binding of clozapine, olanzapine and/or haloperidol to selected receptors involved in body weight regulation. Pharmacogenomics J. 2007 Aug;7(4):275-81. Epub 2006 Sep 19. [16983399 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name:
ABCB1
Uniprot ID:
P08183
Molecular Weight:
141477.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC505.3 uMNot AvailableBindingDB 21398
References
  1. Pajeva IK, Wiese M: Pharmacophore model of drugs involved in P-glycoprotein multidrug resistance: explanation of structural variety (hypothesis). J Med Chem. 2002 Dec 19;45(26):5671-86. [12477351 ]
General Function:
Secondary active organic cation transmembrane transporter activity
Specific Function:
Translocates a broad array of organic cations with various structures and molecular weights including the model compounds 1-methyl-4-phenylpyridinium (MPP), tetraethylammonium (TEA), N-1-methylnicotinamide (NMN), 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP), the endogenous compounds choline, guanidine, histamine, epinephrine, adrenaline, noradrenaline and dopamine, and the drugs quinine, and metformin. The transport of organic cations is inhibited by a broad array of compounds like tetramethylammonium (TMA), cocaine, lidocaine, NMDA receptor antagonists, atropine, prazosin, cimetidine, TEA and NMN, guanidine, cimetidine, choline, procainamide, quinine, tetrabutylammonium, and tetrapentylammonium. Translocates organic cations in an electrogenic and pH-independent manner. Translocates organic cations across the plasma membrane in both directions. Transports the polyamines spermine and spermidine. Transports pramipexole across the basolateral membrane of the proximal tubular epithelial cells. The choline transport is activated by MMTS. Regulated by various intracellular signaling pathways including inhibition by protein kinase A activation, and endogenously activation by the calmodulin complex, the calmodulin-dependent kinase II and LCK tyrosine kinase.
Gene Name:
SLC22A1
Uniprot ID:
O15245
Molecular Weight:
61153.345 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50141.9 uMNot AvailableBindingDB 21398
References
  1. Ahlin G, Karlsson J, Pedersen JM, Gustavsson L, Larsson R, Matsson P, Norinder U, Bergstrom CA, Artursson P: Structural requirements for drug inhibition of the liver specific human organic cation transport protein 1. J Med Chem. 2008 Oct 9;51(19):5932-42. doi: 10.1021/jm8003152. Epub 2008 Sep 13. [18788725 ]
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis.
Gene Name:
SLC18A2
Uniprot ID:
Q05940
Molecular Weight:
55712.075 Da
References
  1. Gonzalez AM, Walther D, Pazos A, Uhl GR: Synaptic vesicular monoamine transporter expression: distribution and pharmacologic profile. Brain Res Mol Brain Res. 1994 Mar;22(1-4):219-26. [7912402 ]
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
AC500.63 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 ]
General Function:
Norepinephrine:sodium symporter activity
Specific Function:
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A2
Uniprot ID:
P23975
Molecular Weight:
69331.42 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.15 uMNVS_TR_hNETNovascreen
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 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-linoleic acid and eicosapentanoic acid. Once activated by a ligand, the receptor binds to promoter elements of target genes. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as transcription activator for the acyl-CoA oxidase gene. Decreases expression of NPC1L1 once activated by a ligand.
Gene Name:
PPARD
Uniprot ID:
Q03181
Molecular Weight:
49902.99 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.61 uMATG_PPARd_TRANSAttagene
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 ]
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.10 uMNVS_GPCR_hAdra2CNovascreen
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 ]
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.52 uMNVS_GPCR_hH1Novascreen
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 ]
General Function:
Monoamine transmembrane transporter activity
Specific Function:
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name:
SLC6A3
Uniprot ID:
Q01959
Molecular Weight:
68494.255 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.81 uMNVS_TR_hDATNovascreen
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 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.03 uMATG_PXRE_CISAttagene
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 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
Receptor for endogenous opioids such as beta-endorphin and endomorphin. Receptor for natural and synthetic opioids including morphine, heroin, DAMGO, fentanyl, etorphine, buprenorphin and methadone. Agonist binding to the receptor induces coupling to an inactive GDP-bound heterotrimeric G-protein complex and subsequent exchange of GDP for GTP in the G-protein alpha subunit leading to dissociation of the G-protein complex with the free GTP-bound G-protein alpha and the G-protein beta-gamma dimer activating downstream cellular effectors. The agonist- and cell type-specific activity is predominantly coupled to pertussis toxin-sensitive G(i) and G(o) G alpha proteins, GNAI1, GNAI2, GNAI3 and GNAO1 isoforms Alpha-1 and Alpha-2, and to a lesser extend to pertussis toxin-insensitive G alpha proteins GNAZ and GNA15. They mediate an array of downstream cellular responses, including inhibition of adenylate cyclase activity and both N-type and L-type calcium channels, activation of inward rectifying potassium channels, mitogen-activated protein kinase (MAPK), phospholipase C (PLC), phosphoinositide/protein kinase (PKC), phosphoinositide 3-kinase (PI3K) and regulation of NF-kappa-B. Also couples to adenylate cyclase stimulatory G alpha proteins. The selective temporal coupling to G-proteins and subsequent signaling can be regulated by RGSZ proteins, such as RGS9, RGS17 and RGS4. Phosphorylation by members of the GPRK subfamily of Ser/Thr protein kinases and association with beta-arrestins is involved in short-term receptor desensitization. Beta-arrestins associate with the GPRK-phosphorylated receptor and uncouple it from the G-protein thus terminating signal transduction. The phosphorylated receptor is internalized through endocytosis via clathrin-coated pits which involves beta-arrestins. The activation of the ERK pathway occurs either in a G-protein-dependent or a beta-arrestin-dependent manner and is regulated by agonist-specific receptor phosphorylation. Acts as a class A G-protein coupled receptor (GPCR) which dissociates from beta-arrestin at or near the plasma membrane and undergoes rapid recycling. Receptor down-regulation pathways are varying with the agonist and occur dependent or independent of G-protein coupling. Endogenous ligands induce rapid desensitization, endocytosis and recycling whereas morphine induces only low desensitization and endocytosis. Heterooligomerization with other GPCRs can modulate agonist binding, signaling and trafficking properties. Involved in neurogenesis. Isoform 12 couples to GNAS and is proposed to be involved in excitatory effects. Isoform 16 and isoform 17 do not bind agonists but may act through oligomerization with binding-competent OPRM1 isoforms and reduce their ligand binding activity.
Gene Name:
OPRM1
Uniprot ID:
P35372
Molecular Weight:
44778.855 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.24 uMNVS_GPCR_hOpiate_muNovascreen
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 ]
General Function:
Phosphatidylinositol phospholipase c activity
Specific Function:
The muscarinic acetylcholine receptor mediates various cellular responses, including inhibition of adenylate cyclase, breakdown of phosphoinositides and modulation of potassium channels through the action of G proteins. Primary transducing effect is Pi turnover.
Gene Name:
CHRM5
Uniprot ID:
P08912
Molecular Weight:
60073.205 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.86 uMNVS_GPCR_hM5Novascreen
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 ]
General Function:
Serotonin:sodium symporter activity
Specific Function:
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
SLC6A4
Uniprot ID:
P31645
Molecular Weight:
70324.165 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC503.96 uMNVS_TR_hSERTNovascreen
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 ]
General Function:
Thioesterase binding
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol.
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC505.51 uMNVS_GPCR_hAdra2ANovascreen
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 ]