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Record Information
Version2.0
Creation Date2009-07-21 20:26:24 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2728
Identification
Common NamePhenytoin
ClassSmall Molecule
DescriptionAn anticonvulsant that is used in a wide variety of seizures. It is also an anti-arrhythmic and a muscle relaxant. The mechanism of therapeutic action is not clear, although several cellular actions have been described including effects on ion channels, active transport, and general membrane stabilization. The mechanism of its muscle relaxant effect appears to involve a reduction in the sensitivity of muscle spindles to stretch. Phenytoin has been proposed for several other therapeutic uses, but its use has been limited by its many adverse effects and interactions with other drugs.
Compound Type
  • Amide
  • Amine
  • Anticonvulsant
  • Drug
  • Metabolite
  • Organic Compound
  • Synthetic Compound
  • Voltage-Gated Sodium Channel Blocker
Chemical Structure
Thumb
Synonyms
Synonym
5,5-Diphenyl-imidazolidine-2,4-dione
5,5-Diphenylhydantoin
5,5-diphenylimidazolidine-2,4-dione
5,5-diphenyltetrahydro-1H-2,4-imidazoledione
5,5-Diphenyltetrahydro-1H-2,4-imidazoledione
5,5-Dwufenylohydantoina
Dihydantoin
DILANTIN
Dilantin-125
Diphenylan Sodium
Diphenylhydantoin
Diphenylhydatanoin
Epanutin
Eptoin
Fenitoina
PHENTYTOIN
Phenytek
Phenytoin Sodium
Phenytoine
Phenytoinum
Chemical FormulaC15H12N2O2
Average Molecular Mass252.268 g/mol
Monoisotopic Mass252.090 g/mol
CAS Registry Number57-41-0
IUPAC Name5,5-diphenylimidazolidine-2,4-dione
Traditional Namesilantin
SMILESOC1=NC(C(O)=N1)(C1=CC=CC=C1)C1=CC=CC=C1
InChI IdentifierInChI=1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19)
InChI KeyInChIKey=CXOFVDLJLONNDW-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassImidazolidines
Direct ParentPhenylhydantoins
Alternative Parents
Substituents
  • Diphenylmethane
  • 5-phenylhydantoin
  • Phenylimidazolidine
  • Alpha-amino acid or derivatives
  • 5-monosubstituted hydantoin
  • N-acyl urea
  • Ureide
  • Monocyclic benzene moiety
  • Benzenoid
  • Dicarboximide
  • Urea
  • Carbonic acid derivative
  • Carboxylic acid derivative
  • Azacycle
  • Hydrocarbon derivative
  • Organic oxide
  • Organooxygen compound
  • Organonitrogen compound
  • Organopnictogen compound
  • Organic oxygen compound
  • Carbonyl group
  • Organic nitrogen compound
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point286°C
Boiling PointNot Available
Solubility32 mg/L (at 22°C)
LogP2.47
Predicted Properties
PropertyValueSource
Water Solubility0.071 g/LALOGPS
logP2.26ALOGPS
logP2.15ChemAxon
logS-3.6ALOGPS
pKa (Strongest Acidic)8.49ChemAxon
pKa (Strongest Basic)-9ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area58.2 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity70.18 m³·mol⁻¹ChemAxon
Polarizability25.48 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-003r-7930000000-447969b9c242748dd943JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-0090000000-4176043a7a73caee2667JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0zgi-5960000000-e1dcb47a1c082f04f456JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-1390000000-22c71a7e4dbf9c7acab5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-2190000000-50174e33af92b04d1a6eJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-003r-7930000000-447969b9c242748dd943JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-0090000000-4176043a7a73caee2667JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-0zgi-5960000000-e1dcb47a1c082f04f456JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-1390000000-22c71a7e4dbf9c7acab5JSpectraViewer | MoNA
GC-MSGC-MS Spectrum - CI-B (Non-derivatized)splash10-0udi-2190000000-50174e33af92b04d1a6eJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-00lr-0920000000-edf72a4c297e405a2600JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-001i-0950000000-a80521d4dc3976a29b2cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0ue9-2900000000-a58471ae75fa7319c03dJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0090000000-aaae845342f345f89695JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0390000000-f8da1896c569c120faa2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0920000000-07c872b05aade63c402bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0900000000-be6790637be99260525eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0900000000-9a17fa0b243c8282f3baJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , negativesplash10-0udi-0900000000-69302626996b2b24c153JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0fai-0690000000-f9eeceb82d117127f6eaJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0910000000-9edcfc62014a6aa7778fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-001i-0900000000-d4dde5db680fb7722a49JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0ue9-0900000000-482874b33812389ae726JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0900000000-44f07dc29daf8cdf80c2JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-1900000000-1241292d531ed37544c7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0950000000-a80521d4dc3976a29b2cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0ue9-2900000000-a58471ae75fa7319c03dJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0udi-0290000000-168825c4263cc790be0bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0f89-0950000000-27e345a92f7734114654JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0uyi-1900000000-5828317e8dac2d03e548JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0udi-0090000000-e1551530faa59a549515JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udi-1190000000-354c210fa308dab349f3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9700000000-d5833bfc084997249fe4JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0f89-4940000000-2a0dda513d9f63dc6610JSpectraViewer | MoNA
1D NMR1H NMR SpectrumNot AvailableJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureIntravenous, Oral, Intramuscular. Bioavailability 70-100% oral, 24.4% for rectal and intravenous administration. Rapid rate of absorption with peak blood concentration expected in 1½ to 3 hours.
Mechanism of ToxicityPhenytoin acts on sodium channels on the neuronal cell membrane, limiting the spread of seizure activity and reducing seizure propagation. By promoting sodium efflux from neurons, phenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of post-tetanic potentiation at synapses. Loss of post-tetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas.
MetabolismPrimarily hepatic. The majority of the dose (up to 90%) is metabolized to 5-(4'-hydroxyphenyl)-5-phenylhydantoin (p-HPPH). This metabolite undergoes further glucuronidation and is excreted into the urine. CYP2C19 and CYP2C9 catalyze the aforementioned reaction. Route of Elimination: Most of the drug is excreted in the bile as inactive metabolites which are then reabsorbed from the intestinal tract and excreted in the urine. Urinary excretion of phenytoin and its metabolites occurs partly with glomerular filtration but, more importantly, by tubular secretion. Half Life: 22 hours (range of 7 to 42 hours)
Toxicity ValuesOral, mouse: LD50 = 150 mg/kg; Oral, rat: LD50 = 1635 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)2B, possibly carcinogenic to humans. (5)
Uses/SourcesFor the control of generalized tonic-clonic (grand mal) and complex partial (psychomotor, temporal lobe) seizures and prevention and treatment of seizures occurring during or following neurosurgery.
Minimum Risk LevelNot Available
Health EffectsMay cause a potentially dangerous rash that may develop into Stevens Johnson syndrome, an extremely rare but potentially fatal skin disease.
SymptomsSymptoms of overdose include coma, difficulty in pronouncing words correctly, involuntary eye movement, lack of muscle coordination, low blood pressure, nausea, sluggishness, slurred speech, tremors, and vomiting.
TreatmentTreatment is nonspecific since there is no known antidote. The adequacy of the respiratory and circulatory systems should be carefully observed and appropriate supportive measures employed. Hemodialysis can be considered since phenytoin is not completely bound to plasma proteins. Total exchange transfusion has been used in the treatment of severe intoxication in pediatric patients. (3)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00252
HMDB IDHMDB14397
PubChem Compound ID1775
ChEMBL IDCHEMBL16
ChemSpider ID1710
KEGG IDC07443
UniProt IDNot Available
OMIM ID
ChEBI ID8107
BioCyc IDNot Available
CTD IDNot Available
Stitch IDPhenytoin
PDB IDNot Available
ACToR ID549
Wikipedia LinkPhenytoin
References
Synthesis Reference

Mahdi B. Fawzi, Anne K. Taylor, “Parenteral phenytoin preparations.” U.S. Patent US4642316, issued April, 1981.

MSDSLink
General References
  1. https://www.pharmgkb.org/pathway/PA145011115
  2. Drugs.com [Link]
  3. RxList: The Internet Drug Index (2009). [Link]
  4. PharmGKB [Link]
  5. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails
Down-Regulated Genes
GeneGene SymbolGene IDInteractionChromosomeDetails

Targets

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
AC500.02 uMNVS_NR_hPXRNovascreen
References
  1. Faucette SR, Wang H, Hamilton GA, Jolley SL, Gilbert D, Lindley C, Yan B, Negishi M, LeCluyse EL: Regulation of CYP2B6 in primary human hepatocytes by prototypical inducers. Drug Metab Dispos. 2004 Mar;32(3):348-58. [14977870 ]
  2. Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [15039302 ]
  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 sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is responsible for the initial upstroke of the action potential. Channel inactivation is regulated by intracellular calcium levels.
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50003655
References
  1. Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. [15066664 ]
  2. Swadron SP, Rudis MI, Azimian K, Beringer P, Fort D, Orlinsky M: A comparison of phenytoin-loading techniques in the emergency department. Acad Emerg Med. 2004 Mar;11(3):244-52. [15001403 ]
  3. Davis GC, Kong Y, Paige M, Li Z, Merrick EC, Hansen T, Suy S, Wang K, Dakshanamurthy S, Cordova A, McManus OB, Williams BS, Chruszcz M, Minor W, Patel MK, Brown ML: Asymmetric synthesis and evaluation of a hydroxyphenylamide voltage-gated sodium channel blocker in human prostate cancer xenografts. Bioorg Med Chem. 2012 Mar 15;20(6):2180-8. doi: 10.1016/j.bmc.2011.08.061. Epub 2011 Sep 1. [22364743 ]
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
Inhibitory6 uMNot AvailableBindingDB 50003655
Inhibitory10 uMNot AvailableBindingDB 50003655
References
  1. Afzelius L, Zamora I, Masimirembwa CM, Karlen A, Andersson TB, Mecucci S, Baroni M, Cruciani G: Conformer- and alignment-independent model for predicting structurally diverse competitive CYP2C9 inhibitors. J Med Chem. 2004 Feb 12;47(4):907-14. [14761192 ]
  2. Rao S, Aoyama R, Schrag M, Trager WF, Rettie A, Jones JP: A refined 3-dimensional QSAR of cytochrome P450 2C9: computational predictions of drug interactions. J Med Chem. 2000 Jul 27;43(15):2789-96. [10956186 ]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN1A
Uniprot ID:
P35498
Molecular Weight:
228969.49 Da
References
  1. Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB: Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin. Proc Natl Acad Sci U S A. 2005 Apr 12;102(15):5507-12. Epub 2005 Apr 1. [15805193 ]
  2. Tate SK, Singh R, Hung CC, Tai JJ, Depondt C, Cavalleri GL, Sisodiya SM, Goldstein DB, Liou HH: A common polymorphism in the SCN1A gene associates with phenytoin serum levels at maintenance dose. Pharmacogenet Genomics. 2006 Oct;16(10):721-6. [17001291 ]
General Function:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN2A
Uniprot ID:
Q99250
Molecular Weight:
227972.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50>100 uMNot AvailableBindingDB 50003655
References
  1. Fantini M, Rivara M, Zuliani V, Kalmar CL, Vacondio F, Silva C, Baheti AR, Singh N, Merrick EC, Katari RS, Cocconcelli G, Ghiron C, Patel MK: 2,4(5)-diarylimidazoles as inhibitors of hNaV1.2 sodium channels: pharmacological evaluation and structure-property relationships. Bioorg Med Chem. 2009 May 15;17(10):3642-8. doi: 10.1016/j.bmc.2009.03.067. Epub 2009 Apr 10. [19394229 ]
  2. Zuliani V, Fantini M, Nigam A, Stables JP, Patel MK, Rivara M: Anticonvulsant activity of 2,4(1H)-diarylimidazoles in mice and rats acute seizure models. Bioorg Med Chem. 2010 Nov 15;18(22):7957-65. doi: 10.1016/j.bmc.2010.09.029. Epub 2010 Sep 22. [20943396 ]
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
IC50240 uMNot AvailableBindingDB 50003655
References
  1. 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:
Voltage-gated sodium channel activity
Specific Function:
Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient.
Gene Name:
SCN3A
Uniprot ID:
Q9NY46
Molecular Weight:
226291.905 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5018.5 uMNot AvailableBindingDB 50003655
References
  1. Waters JA, Hollingsworth EB, Daly JW, Lewandowski G, Creveling CR: Anticonvulsant activity of piperidinol and (dialkylamino)alkanol esters. J Med Chem. 1986 Aug;29(8):1512-6. [3016269 ]
General Function:
Voltage-gated sodium channel activity
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. This sodium channel may be present in both denervated and innervated skeletal muscle.
Gene Name:
SCN4A
Uniprot ID:
P35499
Molecular Weight:
208059.175 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory24 uMNot AvailableBindingDB 50003655
References
  1. Yang J, Gharagozloo P, Yao J, Ilyin VI, Carter RB, Nguyen P, Robledo S, Woodward RM, Hogenkamp DJ: 3-(4-phenoxyphenyl)pyrazoles: a novel class of sodium channel blockers. J Med Chem. 2004 Mar 11;47(6):1547-52. [14998340 ]
General Function:
Zinc ion binding
Specific Function:
Ligand-activated transcription factor. Receptor for bile acids such as chenodeoxycholic acid, lithocholic acid and deoxycholic acid. Represses the transcription of the cholesterol 7-alpha-hydroxylase gene (CYP7A1) through the induction of NR0B2 or FGF19 expression, via two distinct mechanisms. Activates the intestinal bile acid-binding protein (IBABP). Activates the transcription of bile salt export pump ABCB11 by directly recruiting histone methyltransferase CARM1 to this locus.
Gene Name:
NR1H4
Uniprot ID:
Q96RI1
Molecular Weight:
55913.915 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC501.85 uMNVS_NR_hFXR_AntagonistNovascreen
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
AC507.07 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 ]