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Record Information
Version2.0
Creation Date2009-07-21 20:26:17 UTC
Update Date2014-12-24 20:25:50 UTC
Accession NumberT3D2713
Identification
Common NameReserpine
ClassSmall Molecule
DescriptionAn alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use.
Compound Type
  • Adrenergic Antagonist
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antihypertensive Agent
  • Antipsychotic Agent
  • Drug
  • Ester
  • Ether
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Peripheral Adrenergic Inhibitor
Chemical Structure
Thumb
Synonyms
Synonym
(-)-Reserpine
(3beta,16beta,17alpha,18beta,20alpha)-11,17-Dimethoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]yohimban-16-carboxylic acid methyl ester
(−)-reserpine
3,4,5-trimethoxybenzoyl methyl reserpate
Apoplon
Hiserpia
Novoreserpine
Reserfia
Reserpin
Serpalan
Serpanray
Serpasil
Chemical FormulaC33H40N2O9
Average Molecular Mass608.679 g/mol
Monoisotopic Mass608.273 g/mol
CAS Registry Number50-55-5
IUPAC Namemethyl (1R,15S,17R,18R,19S,20S)-6,18-dimethoxy-17-(3,4,5-trimethoxybenzoyloxy)-3,13-diazapentacyclo[11.8.0.0²,¹⁰.0⁴,⁹.0¹⁵,²⁰]henicosa-2(10),4(9),5,7-tetraene-19-carboxylate
Traditional Namereserpine
SMILES[H][C@@]12CN3CCC4=C(NC5=C4C=CC(OC)=C5)[C@@]3([H])C[C@]1([H])[C@]([H])(C(=O)OC)[C@@]([H])(OC)[C@@]([H])(C2)OC(=O)C1=CC(OC)=C(OC)C(OC)=C1
InChI IdentifierInChI=1S/C33H40N2O9/c1-38-19-7-8-20-21-9-10-35-16-18-13-27(44-32(36)17-11-25(39-2)30(41-4)26(12-17)40-3)31(42-5)28(33(37)43-6)22(18)15-24(35)29(21)34-23(20)14-19/h7-8,11-12,14,18,22,24,27-28,31,34H,9-10,13,15-16H2,1-6H3/t18-,22+,24-,27-,28+,31+/m1/s1
InChI KeyInChIKey=QEVHRUUCFGRFIF-MDEJGZGSSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as yohimbine alkaloids. These are alkaloids containing the pentacyclic yohimban skeleton. The Yohimbinoid alkaloids contain a carbocyclic ring E arising through C-17 to C-18 bond formation in a corynantheine precursor.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassYohimbine alkaloids
Sub ClassNot Available
Direct ParentYohimbine alkaloids
Alternative Parents
Substituents
  • Yohimbine
  • Corynanthean skeleton
  • Yohimbine alkaloid
  • Pyridoindole
  • Beta-carboline
  • Gallic acid or derivatives
  • P-methoxybenzoic acid or derivatives
  • M-methoxybenzoic acid or derivatives
  • Benzoate ester
  • 3-alkylindole
  • Indole
  • Indole or derivatives
  • Benzoic acid or derivatives
  • Benzoyl
  • Phenol ether
  • Anisole
  • Phenoxy compound
  • Methoxybenzene
  • Alkyl aryl ether
  • Aralkylamine
  • Monocyclic benzene moiety
  • Dicarboxylic acid or derivatives
  • Benzenoid
  • Piperidine
  • Pyrrole
  • Methyl ester
  • Heteroaromatic compound
  • Tertiary aliphatic amine
  • Amino acid or derivatives
  • Tertiary amine
  • Carboxylic acid ester
  • Organoheterocyclic compound
  • Ether
  • Carboxylic acid derivative
  • Azacycle
  • Dialkyl ether
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic nitrogen compound
  • Carbonyl group
  • Organic oxygen compound
  • Amine
  • Organooxygen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic 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 Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point264.5°C
Boiling PointNot Available
Solubility73 mg/L (at 30°C)
LogP3.2
Predicted Properties
PropertyValueSource
Water Solubility0.011 g/LALOGPS
logP4.05ALOGPS
logP3.53ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)16.29ChemAxon
pKa (Strongest Basic)7.56ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area117.78 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity161.42 m³·mol⁻¹ChemAxon
Polarizability66.05 ųChemAxon
Number of Rings6ChemAxon
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)splash10-052b-0944108000-d2416a07c507dd693e2bJSpectraViewer | MoNA
GC-MSGC-MS Spectrum - EI-B (Non-derivatized)splash10-052b-0944108000-d2416a07c507dd693e2bJSpectraViewer | MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0002-0549060000-793104ae04e257941689JSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0006-0000090000-a4f3a4e74644a66e8705JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0006-0000090000-22aa398156f73127b459JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0006-0000090000-1a35ce10a9657b978845JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0006-0000090000-f1a507980fe5d4bc47a4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0108920000-d8cec36e08efb0c1e16eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0000009000-2bafaa3238dfda9f4989JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0916102000-d591ae99a68ca35e63b7JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006t-0911000000-1cb6207a1835b7efb13aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00dj-0910000000-550f1f23f96cefe74849JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-05gi-1910000000-9dd2d1b6087fe8b9d1c9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-1910000000-7038e3a2f74fff79f220JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0a4i-0000009000-ea7c0832701dc10b3266JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0916103000-b1128c59f469bc4d949fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-006t-0911000000-8109e56a0558f3f60659JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-00dj-0910000000-c3773763c7f72b03b234JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-05gi-1910000000-21728d59759dc657e49bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-001i-1910000000-bf727df9cb8b3d8296a0JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0002-0108920000-29c40cb6bef71c53750fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0000009000-0004d3aa672941e611c5JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-0004069000-dbc0a3b6edf66c8683bdJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-054k-0205093000-0c6931938051f0e1a721JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-066r-6438290000-e3ef63fc93c29206b47cJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0a4i-0120029000-1e1e860a71102dcc5e5bJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-092c-0321092000-7fe3c97e8909b5c37599JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-01t9-2940040000-c9fe57795b1118e171f4JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-0002-2943000000-8f7998aa667566277f3fJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureOral
Mechanism of ToxicityReserpine's mechanism of action is through inhibition of the ATP/Mg2+ pump responsible for the sequestering of neurotransmitters into storage vesicles located in the presynaptic neuron. The neurotransmitters that are not sequestered in the storage vesicle are readily metabolized by monoamine oxidase (MAO) causing a reduction in catecholamines.
Metabolism Route of Elimination: Reserpine is extensively metabolized to inactive compounds. It is slowly excreted via the urine and feces.
Toxicity ValuesLD50: 420 mg/kg (Oral, Rat) (6) LD50: 44 mg/kg (Intraperitoneal(parenteral), Rat) (6) LD50: 15 mg/kg (Intravenous(parenteral), Rat) (6) LD50: 200 mg/kg (Oral, Mouse) (6) LD50: 52 mg/kg (Subcutaneous(parenteral), Mouse) (6) LD50: 7 mg/kg (Intraperitoneal(parenteral), Rabbit) (6)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)3, not classifiable as to its carcinogenicity to humans. (8)
Uses/SourcesFoe the treatment of hypertension
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00206
HMDB IDHMDB14351
PubChem Compound ID5770
ChEMBL IDCHEMBL772
ChemSpider ID5566
KEGG IDC06539
UniProt IDNot Available
OMIM ID
ChEBI ID28487
BioCyc IDNot Available
CTD IDNot Available
Stitch IDReserpine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkReserpine
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Five-year findings of the hypertension detection and follow-up program. I. Reduction in mortality of persons with high blood pressure, including mild hypertension. Hypertension Detection and Follow-up Program Cooperative Group. JAMA. 1979 Dec 7;242(23):2562-71. [490882 ]
  2. Effects of treatment on morbidity in hypertension. Results in patients with diastolic blood pressures averaging 115 through 129 mm Hg. JAMA. 1967 Dec 11;202(11):1028-34. [4862069 ]
  3. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. JAMA. 1991 Jun 26;265(24):3255-64. [2046107 ]
  4. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ: The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003 May 21;289(19):2560-72. Epub 2003 May 14. [12748199 ]
  5. Moser M: "Cost containment" in the management of hypertension. Ann Intern Med. 1987 Jul;107(1):107-9. [3592424 ]
  6. 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 ]
  7. Drugs.com [Link]
  8. 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:
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. 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. Sievert MK, Hajipour AR, Ruoho AE: Specific derivatization of the vesicle monoamine transporter with novel carrier-free radioiodinated reserpine and tetrabenazine photoaffinity labels. Anal Biochem. 2007 Aug 1;367(1):68-78. Epub 2007 May 3. [17559790 ]
  4. Naudon L, Leroux-Nicollet I, Raisman-Vozari R, Botton D, Costentin J: Time-course of modifications elicited by reserpine on the density and mRNA synthesis of the vesicular monoamine transporter, and on the density of the membrane dopamine uptake complex. Synapse. 1995 Sep;21(1):29-36. [8525459 ]
  5. Erickson JD, Eiden LE, Hoffman BJ: Expression cloning of a reserpine-sensitive vesicular monoamine transporter. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10993-7. [1438304 ]
  6. 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:
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
Inhibitory0.1 uMNot AvailableBindingDB 50017712
Inhibitory11.5 uMNot AvailableBindingDB 50017712
IC500.5 uMNot AvailableBindingDB 50017712
IC502.1 uMNot AvailableBindingDB 50017712
IC502.6 uMNot AvailableBindingDB 50017712
IC503.02 uMNot AvailableBindingDB 50017712
IC503.236 uMNot AvailableBindingDB 50017712
IC503.9 uMNot AvailableBindingDB 50017712
IC505.3 uMNot AvailableBindingDB 50017712
IC506.1 uMNot AvailableBindingDB 50017712
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Active transport of fluorescent P-glycoprotein substrates: evaluation as markers and interaction with inhibitors. Biochem Biophys Res Commun. 2001 Nov 30;289(2):580-5. [11716514 ]
  2. Muller H, Klinkhammer W, Globisch C, Kassack MU, Pajeva IK, Wiese M: New functional assay of P-glycoprotein activity using Hoechst 33342. Bioorg Med Chem. 2007 Dec 1;15(23):7470-9. Epub 2007 Aug 21. [17890094 ]
  3. 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 ]
  4. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MDR1 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):765-72. [12134945 ]
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
Inhibitory1.832 uMNot AvailableBindingDB 50017712
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
General Function:
Xenobiotic-transporting atpase activity
Specific Function:
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both from mitochondria to cytosol and from cytosol to extracellular space, and cellular export of hemin, and heme. Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. Implicated in the efflux of numerous drugs and xenobiotics: mitoxantrone, the photosensitizer pheophorbide, camptothecin, methotrexate, azidothymidine (AZT), and the anthracyclines daunorubicin and doxorubicin.
Gene Name:
ABCG2
Uniprot ID:
Q9UNQ0
Molecular Weight:
72313.47 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5026.30268 uMNot AvailableBindingDB 50017712
References
  1. Pick A, Muller H, Wiese M: Structure-activity relationships of new inhibitors of breast cancer resistance protein (ABCG2). Bioorg Med Chem. 2008 Sep 1;16(17):8224-36. doi: 10.1016/j.bmc.2008.07.034. Epub 2008 Jul 20. [18678495 ]
General Function:
Transporter activity
Specific Function:
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name:
ABCB11
Uniprot ID:
O95342
Molecular Weight:
146405.83 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5010.2 uMNot AvailableBindingDB 50017712
References
  1. Wang EJ, Casciano CN, Clement RP, Johnson WW: Fluorescent substrates of sister-P-glycoprotein (BSEP) evaluated as markers of active transport and inhibition: evidence for contingent unequal binding sites. Pharm Res. 2003 Apr;20(4):537-44. [12739759 ]
General Function:
Organic anion transmembrane transporter activity
Specific Function:
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name:
ABCC2
Uniprot ID:
Q92887
Molecular Weight:
174205.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory295 uMNot AvailableBindingDB 50017712
References
  1. Tang F, Horie K, Borchardt RT: Are MDCK cells transfected with the human MRP2 gene a good model of the human intestinal mucosa? Pharm Res. 2002 Jun;19(6):773-9. [12134946 ]
General Function:
Serotonin transmembrane transporter activity
Specific Function:
Involved in the transport of biogenic monoamines, such as serotonin, from the cytoplasm into the secretory vesicles of neuroendocrine and endocrine cells.
Gene Name:
SLC18A1
Uniprot ID:
P54219
Molecular Weight:
56256.71 Da
References
  1. Ashe KM, Chiu WL, Khalifa AM, Nicolas AN, Brown BL, De Martino RR, Alexander CP, Waggener CT, Fischer-Stenger K, Stewart JK: Vesicular monoamine transporter-1 (VMAT-1) mRNA and immunoreactive proteins in mouse brain. Neuro Endocrinol Lett. 2011;32(3):253-8. [21712771 ]
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
Inhibitory3.849 uMNot AvailableBindingDB 50017712
References
  1. Toll L, Berzetei-Gurske IP, Polgar WE, Brandt SR, Adapa ID, Rodriguez L, Schwartz RW, Haggart D, O'Brien A, White A, Kennedy JM, Craymer K, Farrington L, Auh JS: Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA Res Monogr. 1998 Mar;178:440-66. [9686407 ]
General Function:
Poly(a) rna binding
Specific Function:
Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Gene Name:
TOP1
Uniprot ID:
P11387
Molecular Weight:
90725.19 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC50160 uMNot AvailableBindingDB 50017712
References
  1. Itoh A, Kumashiro T, Yamaguchi M, Nagakura N, Mizushina Y, Nishi T, Tanahashi T: Indole alkaloids and other constituents of Rauwolfia serpentina. J Nat Prod. 2005 Jun;68(6):848-52. [15974606 ]
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
Inhibitory>10 uMNot AvailableBindingDB 50017712
References
  1. Pristupa ZB, Wilson JM, Hoffman BJ, Kish SJ, Niznik HB: Pharmacological heterogeneity of the cloned and native human dopamine transporter: disassociation of [3H]WIN 35,428 and [3H]GBR 12,935 binding. Mol Pharmacol. 1994 Jan;45(1):125-35. [8302271 ]
General Function:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.90 uMTox21_ERa_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 ]
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
AC502.15 uMATG_PXR_TRANSAttagene
AC501.84 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:
Zinc ion binding
Specific Function:
Orphan receptor that acts as transcription activator in the absence of bound ligand. Binds specifically to an estrogen response element and activates reporter genes controlled by estrogen response elements (By similarity). Induces the expression of PERM1 in the skeletal muscle.
Gene Name:
ESRRG
Uniprot ID:
P62508
Molecular Weight:
51305.485 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.67 uMATG_ERRg_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:
Zinc ion binding
Specific Function:
Nuclear hormone receptor. Transcription factor that mediates the action of vitamin D3 by controlling the expression of hormone sensitive genes. Recruited to promoters via its interaction with BAZ1B/WSTF which mediates the interaction with acetylated histones, an essential step for VDR-promoter association. Plays a central role in calcium homeostasis.
Gene Name:
VDR
Uniprot ID:
P11473
Molecular Weight:
48288.64 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC504.90 uMATG_VDRE_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:
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
AC505.26 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:
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
AC505.67 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:
Nucleoside transmembrane transporter activity
Specific Function:
Mediates both influx and efflux of nucleosides across the membrane (equilibrative transporter). It is sensitive (ES) to low concentrations of the inhibitor nitrobenzylmercaptopurine riboside (NBMPR) and is sodium-independent. It has a higher affinity for adenosine. Inhibited by dipyridamole and dilazep (anticancer chemotherapeutics drugs).
Gene Name:
SLC29A1
Uniprot ID:
Q99808
Molecular Weight:
50218.805 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC506.37 uMNVS_TR_hAdoTNovascreen
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:
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC507.59 uMTox21_AR_BLA_Antagonist_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 ]