Record Information
Version2.0
Creation Date2014-08-29 05:52:03 UTC
Update Date2014-12-24 20:26:42 UTC
Accession NumberT3D4197
Identification
Common Name3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid
ClassSmall Molecule
Description3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid(CMPF) 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. 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid(CMPF) is significantly accumulated in the serum of chronic kidney disease patients and is considered to be a potent uremic toxin There are several minor derivatives of CMPF that have been detected in serum and urine including 3-carboxy-4-methyl-5-pentyl-2-furanpropionic acid, 3-carboxy-4-methyl-5-ethyl-2-furanpropionic acid and 3-carboxy-5-propyl-2-furanpropionic acid. CMPF was first detected in human urine in 1979 and it is believed to be formed from the consumption of fish, vegetables and fruits CMPF is a strong inhibitor of mitochondrial respiration and is associated with thyroid dysfunction CMPF also directly inhibits renal secretion of various drugs and endogenous organic acids by competitively inhibiting OAT3 transporters It is also thought to contribute to various neurological abnormalities because it inhibits the transport of organic acids at the blood-brain barrier (1, 2, 3, 4).
Compound Type
  • Ester
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
Synonyms
Synonym
3-Carboxy-4-methyl-5-propyl-2-furan-propanoate
U(3,3)
Chemical FormulaC12H16O5
Average Molecular Mass240.252 g/mol
Monoisotopic Mass240.100 g/mol
CAS Registry Number86879-39-2
IUPAC Name2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid
Traditional Name2-(2-carboxyethyl)-4-methyl-5-propylfuran-3-carboxylic acid
SMILESCCCC1=C(C)C(C(O)=O)=C(CCC(O)=O)O1
InChI IdentifierInChI=1S/C12H16O5/c1-3-4-8-7(2)11(12(15)16)9(17-8)5-6-10(13)14/h3-6H2,1-2H3,(H,13,14)(H,15,16)
InChI KeyInChIKey=WMCQWXZMVIETAO-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as furanoid fatty acids. These are fatty acids containing a 5-alkylfuran-2-alkanoic acid.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassFatty Acyls
Sub ClassFatty acids and conjugates
Direct ParentFuranoid fatty acids
Alternative Parents
Substituents
  • Furanoid fatty acid
  • Furoic acid or derivatives
  • Furan-3-carboxylic acid
  • Furan-3-carboxylic acid or derivatives
  • Furoic acid
  • Dicarboxylic acid or derivatives
  • Furan
  • Heteroaromatic compound
  • Carboxylic acid derivative
  • Carboxylic acid
  • Oxacycle
  • Organoheterocyclic compound
  • Organic oxide
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological Roles
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 Solubility0.22 g/LALOGPS
logP1.68ALOGPS
logP2.3ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)3.87ChemAxon
pKa (Strongest Basic)-2.9ChemAxon
Physiological Charge-2ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area87.74 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity61.08 m³·mol⁻¹ChemAxon
Polarizability25.26 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-006x-2940000000-c178377899768707f7ef2017-09-20View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00xr-9054000000-b2ed65a9650b6e0bed472017-10-06View 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 , negativesplash10-0002-0900000000-0bcba580e8c7fc7ff28d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , negativesplash10-0002-0900000000-d3d2687cc80d9e20e7a52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0002-0090000000-20d96334f84cb59f97b42017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-000i-0090000000-2e3fb6b1387a1189533e2017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-006x-0590000000-b88aab92167a5dbc423e2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-002b-0920000000-f8bf7e8f3a2f5e6babdd2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0udi-9700000000-8cde6db0deca358c01722016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-000j-0980000000-46874398810fc77285292016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0002-1910000000-3c88cba9dade4657bc112016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0pc0-6900000000-84761c36ced8150db9992016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00dm-0890000000-464423a298584f86963e2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-004i-1930000000-39287c920da37a362af12021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00dr-6900000000-a12a03c9a4db8d16d2812021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-002b-0910000000-057236b313c6ed05bb752021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0udj-0900000000-e17797fad7625863d6b32021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-054k-6900000000-f477479965ef2abe5fc42021-09-24View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, H2O, predicted)Not Available2022-08-20View Spectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as 3-Carboxy-4-methyl-5-propyl-2-furan-propanoic acid 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) (6). 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 (7).
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 IDDB07517
HMDB IDHMDB61112
PubChem Compound ID123979
ChEMBL IDCHEMBL1231562
ChemSpider ID110498
KEGG IDNot Available
UniProt IDNot Available
OMIM ID
ChEBI ID41254
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. Niwa T: Organic acids and the uremic syndrome: protein metabolite hypothesis in the progression of chronic renal failure. Semin Nephrol. 1996 May;16(3):167-82. [8734460 ]
  2. Tsutsumi Y, Deguchi T, Takano M, Takadate A, Lindup WE, Otagiri M: Renal disposition of a furan dicarboxylic acid and other uremic toxins in the rat. J Pharmacol Exp Ther. 2002 Nov;303(2):880-7. [12388676 ]
  3. Niwa T: Recent progress in the analysis of uremic toxins by mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2009 Sep 1;877(25):2600-6. doi: 10.1016/j.jchromb.2008.11.032. Epub 2008 Nov 27. [19083276 ]
  4. Deguchi T, Ohtsuki S, Otagiri M, Takanaga H, Asaba H, Mori S, Terasaki T: Major role of organic anion transporter 3 in the transport of indoxyl sulfate in the kidney. Kidney Int. 2002 May;61(5):1760-8. [11967025 ]
  5. 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 ]
  6. 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 ]
  7. 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

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 ]
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 ]
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 ]