p-Cresol sulfate (T3D4184)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-08-29 05:50:57 UTC
Update Date2014-12-24 20:26:41 UTC
Accession NumberT3D4184
Identification
Common Namep-Cresol sulfate
ClassSmall Molecule
Descriptionp-Cresol sulfate is a uremic toxin. Uremic toxins can be subdivided into three major groups based upon their chemical and physical characteristics: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as the phenols and 3) larger so-called middle-molecules, such as beta2-microglobulin. Chronic exposure of uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease. p-Cresol sulfate is a microbial metabolite that is found in urine and likely derives from secondary metabolism of p-cresol. It appears to be elevated in the urine of individuals with progressive multiple sclerosis p-Cresol sulfate is the major component of urinary MBPLM (myelin basic protein-like material). p-Cresol sulfate is a small protein-bound molecule that is poorly cleared with dialysis and is often considered to be a uremic toxin. Uremic toxins include low-molecular-weight compounds such as indoxyl sulfate, p-cresol sulfate, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid and asymmetric dimethylarginine It has also been linked to cardiovascular disease and oxidative injury. (1, 2).
Compound Type
  • Ester
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
4-Cresol sulfate
4-Cresol sulphate
Mono(4-methylphenyl) Sulfate
P-Cresol sulfate
P-Cresol sulfic acid
p-Cresol sulphate
P-Cresol sulphate
P-Cresol sulphic acid
p-Cresyl sulfate
p-Cresyl sulphate
p-Cresyl-sulfate
p-Cresyl-sulphate
p-Cresylsulfate
p-Cresylsulphate
p-Tolyl sulfate (6CI,7CI)
p-Tolyl sulphate (6CI,7CI)
Para-Cresol sulfate
Para-Cresol sulphate
Sulfuric acid mono(p-tolyl) ester (8CI)
Chemical FormulaC7H8O4S
Average Molecular Mass188.201 g/mol
Monoisotopic Mass188.014 g/mol
CAS Registry Number3233-58-7
IUPAC Name(4-methylphenyl)oxidanesulfonic acid
Traditional Name(4-methylphenyl)oxidanesulfonic acid
SMILESCC1=CC=C(OS(O)(=O)=O)C=C1
InChI IdentifierInChI=1S/C7H8O4S/c1-6-2-4-7(5-3-6)11-12(8,9)10/h2-5H,1H3,(H,8,9,10)
InChI KeyInChIKey=WGNAKZGUSRVWRH-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylsulfates. Phenylsulfates are compounds containing a sulfuric acid group conjugated to a phenyl group.
KingdomOrganic compounds
Super ClassOrganic acids and derivatives
ClassOrganic sulfuric acids and derivatives
Sub ClassArylsulfates
Direct ParentPhenylsulfates
Alternative Parents
Substituents
  • Phenylsulfate
  • Phenoxy compound
  • Toluene
  • Benzenoid
  • Sulfuric acid ester
  • Sulfate-ester
  • Sulfuric acid monoester
  • Monocyclic benzene moiety
  • Organic oxygen compound
  • Organic oxide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility1.58 g/LALOGPS
logP-0.55ALOGPS
logP1.71ChemAxon
logS-2.1ALOGPS
pKa (Strongest Acidic)-2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area63.6 ŲChemAxon
Rotatable Bond Count2ChemAxon
Refractivity43.07 m³·mol⁻¹ChemAxon
Polarizability17.17 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-004m-7970000000-1d52a5deeb555385dd842018-05-25View Spectrum
GC-MSGC-MS Spectrum - GC-EI-TOF (Non-derivatized)splash10-004m-7970000000-1d52a5deeb555385dd842018-05-25View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a4r-5900000000-a697bdc119a940cbfd872017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , negativesplash10-053r-8900000000-d93b8dfbd273b034801f2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-11570a4a776bcf5ec9c32021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-7338e81b9250096b6fc52021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Negativesplash10-004r-9800000000-ac89c33600013a77c1412021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-9b2c2e9cce622bbce4d02016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4r-1900000000-9e92c57df7e82ededa952016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0fb9-9200000000-e8e0a9477934a6c4a93c2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-7983b119ea08e1ce64db2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0a4i-0900000000-956ac4acd6542c4e75d12016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4i-6900000000-2dae39fab819632545a92016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0900000000-c3c2c7c1b4570035b39f2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0006-9700000000-d79f4e77126c3cf9ae262021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-ae3f3f10d7ec0a17d1072021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000i-0900000000-1a8286d1aadcdc168ec62021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000i-0900000000-1a8286d1aadcdc168ec62021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-05o0-9400000000-b79e09b3601b2f9c758d2021-09-23View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-25View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, experimental)Not Available2021-10-10View Spectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as p-Cresol sulfate are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (4). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (5).
MetabolismUremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNaturally produced by the body (endogenous).
Minimum Risk LevelNot Available
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
SymptomsAs a uremic toxin, this compound can cause uremic syndrome. Uremic syndrome may affect any part of the body and can cause nausea, vomiting, loss of appetite, and weight loss. It can also cause changes in mental status, such as confusion, reduced awareness, agitation, psychosis, seizures, and coma. Abnormal bleeding, such as bleeding spontaneously or profusely from a very minor injury can also occur. Heart problems, such as an irregular heartbeat, inflammation in the sac that surrounds the heart (pericarditis), and increased pressure on the heart can be seen in patients with uremic syndrome. Shortness of breath from fluid buildup in the space between the lungs and the chest wall (pleural effusion) can also be present.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDHMDB11635
PubChem Compound ID4615423
ChEMBL IDNot Available
ChemSpider ID3806481
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID82914
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDSNot Available
General References
  1. Cao L, Kirk MC, Coward LU, Jackson P, Whitaker JN: p-Cresol sulfate is the dominant component of urinary myelin basic protein like material. Arch Biochem Biophys. 2000 May 1;377(1):9-21. [10775436 ]
  2. Raff AC, Meyer TW, Hostetter TH: New insights into uremic toxicity. Curr Opin Nephrol Hypertens. 2008 Nov;17(6):560-5. doi: 10.1097/MNH.0b013e32830f45b6. [18941347 ]
  3. Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A: Normal and pathologic concentrations of uremic toxins. J Am Soc Nephrol. 2012 Jul;23(7):1258-70. doi: 10.1681/ASN.2011121175. Epub 2012 May 24. [22626821 ]
  4. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  5. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Klotho
General Function:
Vitamin d binding
Specific Function:
May have weak glycosidase activity towards glucuronylated steroids. However, it lacks essential active site Glu residues at positions 239 and 872, suggesting it may be inactive as a glycosidase in vivo. May be involved in the regulation of calcium and phosphorus homeostasis by inhibiting the synthesis of active vitamin D (By similarity). Essential factor for the specific interaction between FGF23 and FGFR1 (By similarity).The Klotho peptide generated by cleavage of the membrane-bound isoform may be an anti-aging circulating hormone which would extend life span by inhibiting insulin/IGF1 signaling.
Gene Name:
KL
Uniprot ID:
Q9UEF7
Molecular Weight:
116179.815 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details
2. NADPH oxidase 4
General Function:
Superoxide-generating nadph oxidase activity
Specific Function:
Constitutive NADPH oxidase which generates superoxide intracellularly upon formation of a complex with CYBA/p22phox. Regulates signaling cascades probably through phosphatases inhibition. May function as an oxygen sensor regulating the KCNK3/TASK-1 potassium channel and HIF1A activity. May regulate insulin signaling cascade. May play a role in apoptosis, bone resorption and lipolysaccharide-mediated activation of NFKB. May produce superoxide in the nucleus and play a role in regulating gene expression upon cell stimulation. Isoform 3 is not functional. Isoform 5 and isoform 6 display reduced activity.Isoform 4: Involved in redox signaling in vascular cells. Constitutively and NADPH-dependently generates reactive oxygen species (ROS). Modulates the nuclear activation of ERK1/2 and the ELK1 transcription factor, and is capable of inducing nuclear DNA damage. Displays an increased activity relative to isoform 1.
Gene Name:
NOX4
Uniprot ID:
Q9NPH5
Molecular Weight:
66930.995 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]
Target Details
3. Solute carrier family 22 member 8
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenadine. Transports benzylpenicillin (PCG), estrone-3-sulfate (E1S), cimetidine (CMD), 2,4-dichloro-phenoxyacetate (2,4-D), p-amino-hippurate (PAH), acyclovir (ACV) and ochratoxin (OTA).
Gene Name:
SLC22A8
Uniprot ID:
Q8TCC7
Molecular Weight:
59855.585 Da
References
  1. Schulz AM, Terne C, Jankowski V, Cohen G, Schaefer M, Boehringer F, Tepel M, Kunkel D, Zidek W, Jankowski J: Modulation of NADPH oxidase activity by known uraemic retention solutes. Eur J Clin Invest. 2014 Aug;44(8):802-11. doi: 10.1111/eci.12297. [25041433 ]
  2. Young GH, Wu VC: KLOTHO methylation is linked to uremic toxins and chronic kidney disease. Kidney Int. 2012 Apr;81(7):611-2. doi: 10.1038/ki.2011.461. [22419041 ]