Back to Compounds

Showing Compound Indoxyl sulfate (FDB022179)

Record Information
Version1.0
Creation date2011-09-21 00:09:41 UTC
Update date2021-12-06 18:12:33 UTC
Primary IDFDB022179
Secondary Accession NumbersNot Available
Chemical Information
FooDB NameIndoxyl sulfate
DescriptionIndoxyl sulfate, also known as 3-indoxyl sulfate, is a member of the class of organic compounds known as arylsulfates. These are organic compounds containing a sulfate group that carries an aryl group through an ether group. Indoxyl sulfate is a metabolite of the common amino acid tryptophan and is derived through the consumption, digestion and microbial processing of protein-rich foods. Indoxyl sulfate is technically a bacterial co-metabolite, meaning that it is derived from both bacterial and host metabolism. Specifically, it is generated from dietary L-tryptophan which is converted to indole in the large intestine via tryptophanase-expressing gastrointestinal bacteria (PMID: 27102537). The resulting indole is converted to indoxyl in the liver via enzyme-mediated hydroxylation by the CYP450 enzyme CYP2E1 (PMID 11808865). Subsequently, indoxyl is converted into indoxyl sulfate by the SULT1A1 sulfotransferase enzyme in the liver (PMID: 12064372). Indoxyl sulfate has been identified as a uremic toxin according to the European Uremic Toxin Working Group (PMID: 22626821 ) and is classified as a protein-bound uremic solute. Indoxyl sulfate is known to bind to serum albumin (PMID: 22626821), to be transported by the OAT1 transporter (PMID: 34678967) and to be an agonist for the arylhydrocarbon receptor (AhR) (PMID: 32527975). High concentrations of indoxyl sulfate in whole blood or blood plasma are known to be associated with the development and progression of chronic kidney disease (CKD) as well as the development of cardiovascular disease (CVD) in humans and other mammals (PMID: 28754616). As a uremic toxin, indoxyl sulfate is known to stimulate glomerular sclerosis (PMID: 8035108), interstitial fibrosis (PMID: 33138205) and increase the rate of progression of renal failure. Indoxyl sulfate is a known tubular toxin (i.e., a renal tubule toxin) and directly induces apoptotic and necrotic cell death of tubular cells in the kidney (PMID: 33138205). Indoxyl sulfate upregulates signal transducers and activators of transcription 3 phosphorylation leading to increases in TGF-β1, monocyte chemotactic protein-1 and alpha-smooth muscle actin production, all of which participate in interstitial inflammation, renal fibrosis and, consequently, CKD progression (PMID: 33138205). Indoxyl sulfate is also a known cardiotoxin (PMID: 30200452). In plasma, indoxyl sulfate induces endothelial dysfunction by inhibiting endothelial proliferation and migration as well as disrupting wound repair in vitro (PMID: 14717914). Indoxyl sulfate is known to impair angiogenesis by suppressing endothelial cell tube formation and endothelial cell proliferation via chronic aryl hydrocarbon receptor (AhR) activation. Many studies suggest that indoxyl sulfate increases oxidative stress which further exacerbates endothelial dysfunction (PMID: 20876676). This ultimately leads to atherosclerosis, peripheral artery disease and cardiovascular disease, which are common in patients with CKD (PMID: 33456671). In hemodialyzed patients, serum levels of indoxyl sulfate are associated with levels of pentosidine, a marker of carbonyl and oxidative stress (PMID: 14524578). In vitro, indoxyl sulfate increases reactive oxygen species (ROS) production in tubular cells and increases NAD(P)H oxidase activity in endothelial cells (PMID: 29976888). Indoxyl sulfate also strongly decreases the levels of glutathione, one of the most active antioxidant systems of the cell (PMID: 29474405). In addition to its well-known renal toxicity and cardiotoxicity, indoxyl sulfate appears to have osteotoxic, myotoxic and neurotoxic effects. As an osteotoxin, indoxyl sulfate impairs osteoblast function and induces abnormalities of bone turnover (PMID: 28781957). Indoxyl sulfate appears to induce low-turnover bone disease by directly acting on both osteoblasts and osteoclast precursors to suppress bone formation and bone resorption. In vitro studies with mouse osteoblasts have shown that indoxyl sulfate suppresses the gene expression of osterix, osteocalcin, and bone morphogenetic protein 2 (BMP2), thereby inhibiting the formation of mineralized bone nodules, leading to suppressed bone formation (PMID: 28781957). As a myotoxin, indoxyl sulfate appears to induce sarcopenia, which is especially common in patients with CKD. In particular, indoxyl sulfate increases the production of several factors related to skeletal muscle breakdown, including reactive oxygen species (ROS) and inflammatory cytokines (TNF-α, IL-6 and TGF-β1) (PMID: 27549031). It also enhances the production of muscle atrophy-related genes, myostatin and atrogin-1 (PMID: 27549031). As a neurotoxin, indoxyl sulfate appears to disrupt the blood brain barrier. In particular, indoxyl sulfate binds to the aryl hydrocarbon receptor (AhR), which is widely expressed in the central nervous system. The binding of indoxyl sulfate to the AhR leads to blood-brain barrier disruption, which is associated with cognitive impairment in animal models of CKD (PMID: 32527975). Indoxyl sulfate, along with quinolinic acid and kynurenine, are significantly elevated in blood/plasma of individuals with dementia (PMID: 34493657). Recently, indoxyl sulfate has been shown to be associated with altered neural processing (as shown by functional MRI) and the serum abundance of indoxyl sulfate is positively correlated with severity of psychic anxiety in humans (PMID: 34697401).
CAS Number487-94-5
Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
SynonymSource
3-Indolyl hydrogen sulfateChEBI
3-Indolyl sulfateChEBI
3-Indoxyl sulfateChEBI
3-Indoxylsulfuric acidChEBI
IndicanChEBI
indol-3-yl Hydrogen sulfateChEBI
indol-3-yl SulfateChEBI
indol-3-yl SulphateChEBI
Indoxyl sulfic acidChEBI
Indoxyl sulphateChEBI
Indoxyl-3-sulphateChEBI
Indoxylsulfuric acidChEBI
3-Indolyl hydrogen sulfuric acidGenerator
3-Indolyl hydrogen sulphateGenerator
3-Indolyl hydrogen sulphuric acidGenerator
3-Indolyl sulfuric acidGenerator
3-Indolyl sulphateGenerator
3-Indolyl sulphuric acidGenerator
3-Indoxyl sulfuric acidGenerator
3-Indoxyl sulphateGenerator
3-Indoxyl sulphuric acidGenerator
3-IndoxylsulfateGenerator
3-IndoxylsulphateGenerator
3-Indoxylsulphuric acidGenerator
indol-3-yl Hydrogen sulfuric acidGenerator
indol-3-yl Hydrogen sulphateGenerator
indol-3-yl Hydrogen sulphuric acidGenerator
indol-3-yl Sulfuric acidGenerator
indol-3-yl Sulphuric acidGenerator
Indoxyl sulfuric acidGenerator
Indoxyl sulphuric acidGenerator
Indoxyl-3-sulfateGenerator
Indoxyl-3-sulfuric acidGenerator
Indoxyl-3-sulphuric acidGenerator
IndoxylsulfateGenerator
IndoxylsulphateGenerator
Indoxylsulphuric acidGenerator
1H-indol-3-yl Hydrogen sulfateHMDB
1H-indol-3-yl Hydrogen sulphateHMDB
indol-3-OlHMDB
Indican monosodium saltHMDB
Monopotassium salt, indicanHMDB
Monosodium salt, indicanHMDB
Sulfate, indoxylHMDB
Indican monopotassium saltHMDB
1H-indol-3-Ol hydrogen sulfate esterHMDB
3-Sulphooxy-1H-indoleHMDB
Indoxyl sulfateGenerator
Indol-3-olhmdb
Indol-3-yl sulfatehmdb
indol-3-yl sulphatehmdb
Predicted Properties
PropertyValueSource
Water Solubility0.79 g/LALOGPS
logP-0.48ALOGPS
logP1.29ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)-1.8ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area79.39 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity49.12 m³·mol⁻¹ChemAxon
Polarizability19.37 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Chemical FormulaC8H7NO4S
IUPAC name(1H-indol-3-yl)oxidanesulfonic acid
InChI IdentifierInChI=1S/C8H7NO4S/c10-14(11,12)13-8-5-9-7-4-2-1-3-6(7)8/h1-5,9H,(H,10,11,12)
InChI KeyBXFFHSIDQOFMLE-UHFFFAOYSA-N
Isomeric SMILESOS(=O)(=O)OC1=CNC2=CC=CC=C12
Average Molecular Weight213.21
Monoisotopic Molecular Weight213.009578407
Classification
Description Belongs to the class of organic compounds known as arylsulfates. These are organic compounds containing a sulfate group that carries an aryl group through an ether group.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic sulfuric acids and derivatives
Sub ClassArylsulfates
Direct ParentArylsulfates
Alternative Parents
Substituents
  • Arylsulfate
  • Indole
  • Indole or derivatives
  • Substituted pyrrole
  • Sulfuric acid monoester
  • Sulfate-ester
  • Sulfuric acid ester
  • Benzenoid
  • Pyrrole
  • Heteroaromatic compound
  • Organoheterocyclic compound
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect

Health effect:

Disposition

Route of exposure:

Source:

Biological location:

Role

Biological role:

Industrial application:

Foods
  • Dairy products
  • Eggs
  • Meats

    • Grains:

    Nuts and legumes:

    Physico-Chemical Properties - Experimental
    Physico-Chemical Properties - Experimental
    PropertyValueReference
    Physical stateSolid
    Physical DescriptionNot Available
    Mass CompositionNot Available
    Melting PointNot Available
    Boiling PointNot Available
    Experimental Water SolubilityNot Available
    Experimental logPNot Available
    Experimental pKaNot Available
    Isoelectric pointNot Available
    ChargeNot Available
    Optical RotationNot Available
    Spectroscopic UV DataNot Available
    DensityNot Available
    Refractive IndexNot Available
    Spectra
    Spectra
    EI-MS/GC-MS
    TypeDescriptionSplash KeyView
    GC-MSIndoxyl sulfate, non-derivatized, GC-MS Spectrumsplash10-0fk9-1890000000-1ccefb12c0ecb58cd51fSpectrum
    GC-MSIndoxyl sulfate, non-derivatized, GC-MS Spectrumsplash10-0bu0-1940000000-990f3edaa0f09b455534Spectrum
    GC-MSIndoxyl sulfate, non-derivatized, GC-MS Spectrumsplash10-004i-0790000000-bc45c54af242dc72b9dbSpectrum
    Predicted GC-MSIndoxyl sulfate, non-derivatized, Predicted GC-MS Spectrum - 70eV, Positivesplash10-01q9-1920000000-61513ebc6b785c807016Spectrum
    Predicted GC-MSIndoxyl sulfate, non-derivatized, Predicted GC-MS Spectrum - 70eV, PositiveNot AvailableSpectrum
    MS/MS
    TypeDescriptionSplash KeyView
    MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Negative (Annotated)splash10-03di-2090000000-53c9050daddd26dc4b7f2012-07-24View Spectrum
    MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Negative (Annotated)splash10-001i-9200000000-2fa7a5fde4214df01ed22012-07-24View Spectrum
    MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Negative (Annotated)splash10-001i-9000000000-c9eec4c054ae464098ed2012-07-24View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 10V, Negativesplash10-03di-0090000000-3cb045bd6bc8f7f8c2b02012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 20V, Negativesplash10-03e9-6290000000-83be1b2526f53131a6eb2012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 30V, Negativesplash10-001i-9400000000-13c9487183bfd123ac3b2012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 40V, Negativesplash10-001i-9100000000-cf4b2fd59d8e983cb5382012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ (API3000, Applied Biosystems) 50V, Negativesplash10-001i-9000000000-d0f51465d6c4ede36ea42012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF (UPLC Q-Tof Premier, Waters) , Negativesplash10-01si-9350000000-7227b62421572ea4e5f72012-08-31View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03di-0090000000-8fc92d1f6e32863121d32017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-03e9-6290000000-b9b7292552ce2dcfccff2017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9400000000-7348f8347e517b6e1de22017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9100000000-e9a190cf92fcef2641502017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , negativesplash10-001i-9000000000-d0f51465d6c4ede36ea42017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , negativesplash10-01si-9350000000-7227b62421572ea4e5f72017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - , positivesplash10-001i-0900000000-d5c9e813f433f6a44f0f2017-09-14View Spectrum
    MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-2ada8a129d47cf18cf2f2021-09-20View Spectrum
    MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-03e9-8190000000-b7fa2468dad04ce9cf7b2021-09-20View Spectrum
    MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-0059-9300000000-4ef26d7f6ffd8a0309a82021-09-20View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0290000000-bcbb5c8a3311192339392017-07-25View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0159-0910000000-0d28f0b8a4ef10141bf22017-07-25View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-014i-2900000000-a394015845114b618d012017-07-25View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0190000000-6917b03dbdcafea367372017-07-26View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0930000000-6cb7fcdb7b15b9a9e80a2017-07-26View Spectrum
    Predicted MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-4900000000-3b57e4454fb97f3e1a1a2017-07-26View Spectrum
    NMR
    TypeDescriptionView
    1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Spectrum
    1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Spectrum
    1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Spectrum
    1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Spectrum
    2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 600 MHz, H2O, experimental)Spectrum
    ChemSpider ID9840
    ChEMBL IDCHEMBL1233636
    KEGG Compound IDNot Available
    Pubchem Compound ID10258
    Pubchem Substance IDNot Available
    ChEBI ID16700
    Phenol-Explorer IDNot Available
    DrugBank IDDB07992
    HMDB IDHMDB00682
    CRC / DFC (Dictionary of Food Compounds) IDNot Available
    EAFUS IDNot Available
    Dr. Duke IDNot Available
    BIGG IDNot Available
    KNApSAcK IDNot Available
    HET IDIOS
    Food Biomarker OntologyNot Available
    VMH IDNot Available
    Flavornet IDNot Available
    GoodScent IDNot Available
    SuperScent IDNot Available
    Wikipedia IDIndican
    Phenol-Explorer Metabolite IDNot Available
    Duplicate IDSNot Available
    Old DFC IDSNot Available
    Associated Foods
    FoodContent Range AverageReference
    FoodReference
    Biological Effects and Interactions
    Health Effects / BioactivitiesNot Available
    EnzymesNot Available
    PathwaysNot Available
    MetabolismNot Available
    BiosynthesisNot Available
    Organoleptic Properties
    FlavoursNot Available
    Files
    MSDSshow
    References
    Synthesis ReferenceNot Available
    General ReferenceNot Available
    Content Reference