Methylguanidine (T3D4170)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (3)XML
Targets (3)
Record Information
Version2.0
Creation Date2014-08-29 05:49:01 UTC
Update Date2014-12-24 20:26:41 UTC
Accession NumberT3D4170
Identification
Common NameMethylguanidine
ClassSmall Molecule
DescriptionMethylguanidine 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. Methylguanidine (MG) is a guanidine compound deriving from protein catabolism. It is also a product of putrefaction. Methylguanidine is a suspected uraemic toxin that accumulates in renal failure, however it also exhibits anti-inflammatory effects. Methylguanidine is synthesized from creatinine concomitant with the synthesis of hydrogen peroxide from endogenous substrates in peroxisomes. Recent evidence suggests that methylguanidine significantly inhibits iNOS activity and TNF- release. This means that methylguandine can attenuate the degree of inflammation and tissue damage associated with endotoxic shock.
Compound Type
  • Amide
  • Amine
  • Food Toxin
  • Metabolite
  • Natural Compound
  • Organic Compound
  • Uremic Toxin
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
1-Methylguanidine
Methylguanidin
MGX
Monomethyl guanidin
Monomethylguanidine
N-Methylguanidine
N1-Methylguanidine
Chemical FormulaC2H7N3
Average Molecular Mass73.097 g/mol
Monoisotopic Mass73.064 g/mol
CAS Registry Number471-29-4
IUPAC NameN-methylguanidine
Traditional Namemethylguanidine
SMILESCNC(N)=N
InChI IdentifierInChI=1S/C2H7N3/c1-5-2(3)4/h1H3,(H4,3,4,5)
InChI KeyInChIKey=CHJJGSNFBQVOTG-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as guanidines. Guanidines are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.
KingdomOrganic compounds
Super ClassOrganic nitrogen compounds
ClassOrganonitrogen compounds
Sub ClassGuanidines
Direct ParentGuanidines
Alternative Parents
Substituents
  • Guanidine
  • Carboximidamide
  • Organopnictogen compound
  • Hydrocarbon derivative
  • Imine
  • Aliphatic acyclic compound
Molecular FrameworkAliphatic acyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
Biofluid LocationsNot Available
Tissue Locations
  • Brain
  • Liver
PathwaysNot Available
ApplicationsNot Available
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility1.78 mg/mL
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility15.7 g/LALOGPS
logP-1.3ALOGPS
logP-0.96ChemAxon
logS-0.67ALOGPS
pKa (Strongest Basic)12.78ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area61.9 ŲChemAxon
Rotatable Bond Count0ChemAxon
Refractivity30.63 m³·mol⁻¹ChemAxon
Polarizability7.57 ųChemAxon
Number of Rings0ChemAxon
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-9000000000-0b42b86da8534391928a2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-05fr-9000000000-534633b3b3a72158d5162012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-0a4i-9000000000-ee83bc75360621d86cc92012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0006-9000000000-7c1f479fe12182b55b742012-07-24View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-9000000000-44511a31625f714234e52017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-b6d964b0cfb37e04aa3a2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-18c440680d035ed316d42021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-ecb092d7f7fa515ac8812021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-cc59ab6824edf551244e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-052f-9000000000-f836ec6360a96bbbd0542021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-3b8beb22e673f9fe659e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-7ef3fba0b93f0ffa9dbe2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-387fd6ffcb6fd5f260f92021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 10V, Positivesplash10-0ab9-9000000000-d397b15b0bf6997fff622021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 40V, Positivesplash10-0006-9000000000-772b7e2aeeb01889ea682021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-b2d8c441679319b6b93b2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-f6850e9d0e6cc606dd732021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-9000000000-c221ed32014cd06b0bfc2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-9000000000-83eaeeade889a9c4fad42017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-06dl-9000000000-afe740e2160d95afdac82017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00e9-9000000000-471b2da48f84e67fff622017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-9000000000-193b559c768749fc6b0b2017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-3661661b88220d2279072017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0a4i-9000000000-dd30b822725ba557254e2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0a4i-9000000000-f8ebd4faa807cb8f53212021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0a4l-9000000000-eba2529a06eb90d77ce52021-09-22View Spectrum
MSMass Spectrum (Electron Ionization)splash10-007o-9000000000-9397702dbb559840626e2014-09-20View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, H2O, experimental)Not Available2012-12-04View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
2D NMR[1H, 13C]-HSQC NMR Spectrum (2D, 400 MHz, H2O, experimental)Not Available2012-12-05View Spectrum
Toxicity Profile
Route of ExposureEndogenous, Ingestion, Dermal (contact)
Mechanism of ToxicityUremic toxins such as methylguanidine 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) (2). 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 (3).
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 IDHMDB01522
PubChem Compound ID10111
ChEMBL IDNot Available
ChemSpider ID9707
KEGG IDC02294
UniProt IDNot Available
OMIM ID
ChEBI ID16628
BioCyc IDCPD-593
CTD IDNot Available
Stitch IDNot Available
PDB IDMGX
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferencePhilippi, E.; Morsch, K. Preparation of methylguanidine according to Werner-Bell. Berichte der Deutschen Chemischen Gesellschaft [Abteilung] B: Abhandlungen (1927), 60B 2120-2.
MSDSLink
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. De Deyn PP, Marescau B, D'Hooge R, Possemiers I, Nagler J, Mahler C: Guanidino compound levels in brain regions of non-dialyzed uremic patients. Neurochem Int. 1995 Sep;27(3):227-37. [8520461 ]
  5. Lazdins I, Dawborn JK: Concentration of guanidines in normal human plasma. Clin Exp Pharmacol Physiol. 1978 Jan-Feb;5(1):75-80. [639360 ]
  6. De Deyn PP, Marescau B, Cuykens JJ, Van Gorp L, Lowenthal A, De Potter WP: Guanidino compounds in serum and cerebrospinal fluid of non-dialyzed patients with renal insufficiency. Clin Chim Acta. 1987 Jul 30;167(1):81-8. [3665089 ]
  7. Orita Y, Ando A, Tsubakihara Y, Mikami H, Kikuchi T, Nakata K, Abe H: Tissue and blood cell concentration of methylguanidine in rats and patients with chronic renal failure. Nephron. 1981;27(1):35-9. [7219635 ]
  8. Hiraga Y, Kinoshita T: High-performance liquid chromatographic analysis of guanidino compounds using ninhydrin reagent. II. Guanidino compounds in blood of patients on haemodialysis therapy. J Chromatogr. 1985 Aug 9;342(2):269-75. [4055949 ]
  9. Silwood CJ, Lynch E, Claxson AW, Grootveld MC: 1H and (13)C NMR spectroscopic analysis of human saliva. J Dent Res. 2002 Jun;81(6):422-7. [12097436 ]
  10. Boppana VK, Rhodes GR, Brooks DP: Determination of methylguanidine in plasma and urine by high-performance liquid chromatography with fluorescence detection following postcolumn derivatization. Anal Biochem. 1990 Feb 1;184(2):213-8. [2327567 ]
  11. Nohara Y, Hanai T, Suzuki J, Matsumoto G, Iinuma F, Kubo H, Kinoshita T, Watanabe M: Automatic system for the assay of guanidino compounds to assess uremic status. Biol Pharm Bull. 2000 Sep;23(9):1015-20. [10993196 ]
  12. Fujitsuka N, Yokozawa T, Oura H, Akao T, Kobashi K, Ienaga K, Nakamura K: L-gulono-gamma-lactone oxidase is the enzyme responsible for the production of methylguanidine in the rat liver. Nephron. 1993;63(4):445-51. [8459881 ]
  13. Mizutani N, Hayakawa C, Ohya Y, Watanabe K, Watanabe Y, Mori A: Guanidino compounds in hyperargininemia. Tohoku J Exp Med. 1987 Nov;153(3):197-205. [3433275 ]
  14. Giovannetti S, Barsotti G: Uremic intoxication. Nephron. 1975;14(2):123-33. [1093053 ]
  15. Shainkin R, Berkenstadt Y, Giat Y, Berlyne GM: An automated technique for the analysis of plasma guanidino acids, and some findings in chronic renal disease. Clin Chim Acta. 1975 Apr 2;60(1):45-50. [236102 ]
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 ]