General Information

MaintermGUANIDINE
CAS Reg.No.(or other ID)113-00-8
Regnum 176.180
177.1200

From www.fda.gov

Computed Descriptors

Download SDF
2D Structure
CID3520
IUPAC Nameguanidine
InChIInChI=1S/CH5N3/c2-1(3)4/h(H5,2,3,4)
InChI KeyZRALSGWEFCBTJO-UHFFFAOYSA-N
Canonical SMILESC(=N)(N)N
Molecular FormulaCH5N3
Wikipediaguanidine

From Pubchem


Computed Properties

Property Name Property Value
Molecular Weight59.072
Hydrogen Bond Donor Count3
Hydrogen Bond Acceptor Count1
Rotatable Bond Count0
Complexity26.3
CACTVS Substructure Key Fingerprint A A A D c Y A D A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A B A A Q A A A A A A A A A A A B A A B A A A A g A A A A I A A A A A C A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area75.9
Monoisotopic Mass59.048
Exact Mass59.048
XLogP3None
XLogP3-AA-1.3
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count4
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem


ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.8502
Human Intestinal AbsorptionHIA+0.9378
Caco-2 PermeabilityCaco2-0.7527
P-glycoprotein SubstrateNon-substrate0.8033
P-glycoprotein InhibitorNon-inhibitor0.9770
Non-inhibitor0.9320
Renal Organic Cation TransporterNon-inhibitor0.7825
Distribution
Subcellular localizationLysosome0.5748
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8402
CYP450 2D6 SubstrateNon-substrate0.6619
CYP450 3A4 SubstrateNon-substrate0.8447
CYP450 1A2 InhibitorNon-inhibitor0.9843
CYP450 2C9 InhibitorNon-inhibitor0.9588
CYP450 2D6 InhibitorNon-inhibitor0.9695
CYP450 2C19 InhibitorNon-inhibitor0.9772
CYP450 3A4 InhibitorNon-inhibitor0.9763
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9789
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9733
Non-inhibitor0.9798
AMES ToxicityNon AMES toxic0.9133
CarcinogensNon-carcinogens0.7148
Fish ToxicityLow FHMT0.8795
Tetrahymena Pyriformis ToxicityHigh TPT0.5784
Honey Bee ToxicityLow HBT0.5000
BiodegradationNot ready biodegradable0.7652
Acute Oral ToxicityII0.5514
Carcinogenicity (Three-class)Non-required0.6807

From admetSAR


ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility-0.0870LogS
Caco-2 Permeability0.4633LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity1.9367LD50, mol/kg
Fish Toxicity2.4000pLC50, mg/L
Tetrahymena Pyriformis Toxicity0.0045pIGC50, ug/L

From admetSAR


Toxicity Profile

Route of ExposureRapidly absorbed and distributed
Mechanism of ToxicityUremic toxins such as guaniidine 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) . 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 .
MetabolismNot metabolized. Half Life: 7-8 hours
Toxicity ValuesLD<sub>50</sub> = 475 mg/kg (oral, rat).
Lethal DoseNone
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelNone
Health EffectsChronic exposure to uremic toxins can lead to a number of conditions including renal damage, chronic kidney disease and cardiovascular disease.
TreatmentKidney dialysis is usually needed to relieve the symptoms of uremic syndrome until normal kidney function can be restored.
Reference
  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. 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 ]
  3. 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 ]
  4. 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 ]
  5. Grundemann D, Liebich G, Kiefer N, Koster S, Schomig E: Selective substrates for non-neuronal monoamine transporters. Mol Pharmacol. 1999 Jul;56(1):1-10.[10385678 ]
  6. 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 ]
  7. Bullough A, Karadia S, Watters M: Phaeochromocytoma: an unusual cause of hypertension in pregnancy. Anaesthesia. 2001 Jan;56(1):43-6.[11167434 ]
  8. Mannik M, Person RE: Deep penetration of antibodies into the articular cartilage of patients with rheumatoid arthritis. Rheumatol Int. 1994;14(3):95-102.[7839077 ]
  9. Eropkin MIu, Smirnova TD, Eropkina EM, Mamaeva EG: [The study of the Ca2+ role in cytotoxic response of human cells in culture to the action of xenobiotics]. Tsitologiia. 2000;42(2):154-9.[10752119 ]
  10. Rufanova VA, Sorokin A: CrkII associates with BCAR3 in response to endothelin-1 in human glomerular mesangial cells. Exp Biol Med (Maywood). 2006 Jun;231(6):752-6.[16740993 ]
  11. Bjornsson S: Size-dependent separation of proteoglycans by electrophoresis in gels of pure agarose. Anal Biochem. 1993 May 1;210(2):292-8.[8512064 ]
  12. Sakamoto N, Toge T, Nishiyama M: Tumor-specific synergistic therapy of mitomycin C: modulation of bioreductive activation. Hiroshima J Med Sci. 1997 Jun;46(2):67-73.[9232934 ]
  13. Lorenzo P, Bayliss MT, Heinegard D: A novel cartilage protein (CILP) present in the mid-zone of human articular cartilage increases with age. J Biol Chem. 1998 Sep 4;273(36):23463-8.[9722583 ]
  14. Dabaghian RH, Barnard G, McConnell I, Clewley JP: An immunoassay for the pathological form of the prion protein based on denaturation and time resolved fluorometry. J Virol Methods. 2006 Mar;132(1-2):85-91. Epub 2005 Oct 10.[16219367 ]
  15. Gothert M, Bruss M, Bonisch H, Molderings GJ: Presynaptic imidazoline receptors. New developments in characterization and classification. Ann N Y Acad Sci. 1999 Jun 21;881:171-84.[10415912 ]
  16. Okumi M, Ueda T, Ichimaru N, Fujimoto N, Itoh K: [A case of composite pheochromocytoma-ganglioneuroblastoma in the adrenal gland with primary hyperparathyroidism]. Hinyokika Kiyo. 2003 May;49(5):269-72.[12822455 ]
  17. Leitersdorf E, Reshef A, Meiner V, Levitzki R, Schwartz SP, Dann EJ, Berkman N, Cali JJ, Klapholz L, Berginer VM: Frameshift and splice-junction mutations in the sterol 27-hydroxylase gene cause cerebrotendinous xanthomatosis in Jews or Moroccan origin. J Clin Invest. 1993 Jun;91(6):2488-96.[8514861 ]
  18. Atlas D: Molecular and physiological properties of clonidine-displacing substance. Ann N Y Acad Sci. 1995 Jul 12;763:314-24.[7677341 ]
  19. Rubello D, Bui C, Casara D, Gross MD, Fig LM, Shapiro B: Functional scintigraphy of the adrenal gland. Eur J Endocrinol. 2002 Jul;147(1):13-28.[12088915 ]
  20. Wang JG, Lemon SM: Hepatitis delta virus antigen forms dimers and multimeric complexes in vivo. J Virol. 1993 Jan;67(1):446-54.[7677957 ]
  21. Maruta K, Sonoda Y, Saigo R, Yoshioka T, Fukunaga H: [A patient with von Recklinghausen's disease associated with polymyositis, asymptomatic pheochromocytoma, and primary hepatic leiomyosarcoma]. Nihon Ronen Igakkai Zasshi. 2004 May;41(3):339-43.[15237755 ]
  22. Noyori K, Koshino T, Takagi T, Okamoto R, Jasin HE: Binding characteristics of antitype II collagen antibody to the surface of diseased human cartilage as a probe for tissue damage. J Rheumatol. 1994 Feb;21(2):293-6.[8182639 ]
  23. Tapiero H, Mathe G, Couvreur P, Tew KD: I. Arginine. Biomed Pharmacother. 2002 Nov;56(9):439-45.[12481980 ]

From T3DB


Taxonomic Classification

KingdomOrganic compounds
SuperclassOrganic nitrogen compounds
ClassOrganonitrogen compounds
SubclassGuanidines
Intermediate Tree NodesNot available
Direct ParentGuanidines
Alternative Parents
Molecular FrameworkAliphatic acyclic compounds
SubstituentsGuanidine - Carboximidamide - Organopnictogen compound - Hydrocarbon derivative - Imine - Aliphatic acyclic compound
DescriptionThis compound belongs to the class of organic compounds known as guanidines. These are compounds containing a guanidine moiety, with the general structure (R1R2N)(R3R4N)C=N-R5.

From ClassyFire


Targets

General Function:
Methyltransferase activity
Gene Name:
GAMT
Uniprot ID:
Q14353
Molecular Weight:
26317.925 Da
References
  1. 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:
Scaffold protein binding
Specific Function:
Interacts with the cytoplasmic tail of NMDA receptor subunits and shaker-type potassium channels. Required for synaptic plasticity associated with NMDA receptor signaling. Overexpression or depletion of DLG4 changes the ratio of excitatory to inhibitory synapses in hippocampal neurons. May reduce the amplitude of ASIC3 acid-evoked currents by retaining the channel intracellularly. May regulate the intracellular trafficking of ADR1B (By similarity).
Gene Name:
DLG4
Uniprot ID:
P78352
Molecular Weight:
80494.615 Da
References
  1. 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:
Electron carrier activity
Gene Name:
ALDH2
Uniprot ID:
P05091
Molecular Weight:
56380.93 Da
References
  1. 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:
Ribonuclease a activity
Specific Function:
Endonuclease that catalyzes the cleavage of RNA on the 3' side of pyrimidine nucleotides. Acts on single-stranded and double-stranded RNA.
Gene Name:
RNASE1
Uniprot ID:
P07998
Molecular Weight:
17644.125 Da
References
  1. 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:
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. 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. 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. 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:
Atp binding
Gene Name:
argG
Uniprot ID:
P0A6E4
Molecular Weight:
49898.01 Da
General Function:
Lysozyme activity
Specific Function:
Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.
Gene Name:
E
Uniprot ID:
P00720
Molecular Weight:
18691.385 Da
General Function:
Metal ion binding
Specific Function:
Controls arginine catabolism.
Gene Name:
rocF
Uniprot ID:
P53608
Molecular Weight:
32432.98 Da

From T3DB