Basic Info

Common NameHypoxanthine(F05237)
2D Structure
Description

Hypoxanthine 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.
Hypoxanthine is a naturally occurring purine derivative and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. Hypoxanthine is also a spontaneous deamination product of adenine. Lesch-Nyhan disease is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase.

FRCD IDF05237
CAS Number68-94-0
PubChem CID790
FormulaC5H4N4O
IUPAC Name

3,7-dihydropurin-6-one

InChI Key

FDGQSTZJBFJUBT-UHFFFAOYSA-N

InChI

InChI=1S/C5H4N4O/c10-5-3-4(7-1-6-3)8-2-9-5/h1-2H,(H2,6,7,8,9,10)

Canonical SMILES

C1=NC2=C(N1)C(=O)N=CN2

Isomeric SMILES

C1=NC2=C(N1)C(=O)N=CN2

WikipediaHypoxanthine
Synonyms
        
            Sarkin
        
            Sarcine
        
            Purin-6(1H)-one
        
            hypoxanthine
        
            68-94-0
        
            6-Hydroxypurine
        
            9H-Purin-6-ol
        
            6-Oxopurine
        
            Sarkine
        
            Purin-6-ol
        
Classifies
                

                  
                    Predicted: Animal Toxin
                  

                
        
Update DateNov 13, 2018 17:07

Chemical Taxonomy

KingdomOrganic compounds
SuperclassOrganoheterocyclic compounds
ClassImidazopyrimidines
SubclassPurines and purine derivatives
Intermediate Tree NodesPurinones
Direct ParentHypoxanthines
Alternative Parents
Molecular FrameworkAromatic heteropolycyclic compounds
Substituents6-oxopurine - Hypoxanthine - Pyrimidone - Pyrimidine - Azole - Imidazole - Vinylogous amide - Heteroaromatic compound - Azacycle - Organic oxide - Organopnictogen compound - Organooxygen compound - Organonitrogen compound - Organic nitrogen compound - Organic oxygen compound - Hydrocarbon derivative - Aromatic heteropolycyclic compound
DescriptionThis compound belongs to the class of organic compounds known as hypoxanthines. These are compounds containing the purine derivative 1H-purin-6(9H)-one. Purine is a bicyclic aromatic compound made up of a pyrimidine ring fused to an imidazole ring.

Properties

Property NameProperty Value
Molecular Weight136.114
Hydrogen Bond Donor Count2
Hydrogen Bond Acceptor Count2
Rotatable Bond Count0
Complexity190
Monoisotopic Mass136.039
Exact Mass136.039
XLogP-1.1
Formal Charge0
Heavy Atom Count10
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

ADMET

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9681
Human Intestinal AbsorptionHIA+0.9874
Caco-2 PermeabilityCaco2-0.7137
P-glycoprotein SubstrateNon-substrate0.6266
P-glycoprotein InhibitorNon-inhibitor0.9574
Non-inhibitor0.9893
Renal Organic Cation TransporterNon-inhibitor0.9095
Distribution
Subcellular localizationMitochondria0.4537
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8174
CYP450 2D6 SubstrateNon-substrate0.7724
CYP450 3A4 SubstrateNon-substrate0.6637
CYP450 1A2 InhibitorInhibitor0.6341
CYP450 2C9 InhibitorNon-inhibitor0.8791
CYP450 2D6 InhibitorNon-inhibitor0.8952
CYP450 2C19 InhibitorNon-inhibitor0.8152
CYP450 3A4 InhibitorNon-inhibitor0.9184
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.9240
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9766
Non-inhibitor0.9168
AMES ToxicityNon AMES toxic0.7018
CarcinogensNon-carcinogens0.9703
Fish ToxicityLow FHMT0.6451
Tetrahymena Pyriformis ToxicityHigh TPT0.6678
Honey Bee ToxicityLow HBT0.6668
BiodegradationNot ready biodegradable0.8456
Acute Oral ToxicityIII0.6532
Carcinogenicity (Three-class)Non-required0.7232

Model Value Unit
Absorption
Aqueous solubility-2.6172LogS
Caco-2 Permeability0.4631LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.2365LD50, mol/kg
Fish Toxicity2.4182pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.0074pIGC50, ug/L

References

TitleJournalDatePubmed ID
Synthesis, characterization and xanthine oxidase inhibition of Cu(II)-chrysincomplex.Spectrochim Acta A Mol Biomol Spectrosc2017 May 528167361
Potent mutagenicity of some non-planar tri- and tetrachlorinated biphenyls in mammalian cells, human CYP2E1 being a major activating enzyme.Arch Toxicol2017 Jul27913846
Mass Spectrometry-Based Metabolomic and Lipidomic Analyses of the Effects ofDietary Platycodon grandiflorum on Liver and Serum of Obese Mice under a High-FatDiet.Nutrients2017 Jan 1728106735
Induction of cytotoxic and genotoxic damage following exposure of V79 cells to cadmium chloride.Mutat Res Genet Toxicol Environ Mutagen2017 Apr28464991
Effect of Sugar on the Changes in Quality of Lightly Salted Grass Carp(Ctenopharyngodon idellus) Fillets under Vacuum Packaging at 4°C.J Food Prot2016 Mar26939658
Wayanin and guaijaverin, two active metabolites found in a Psidium acutangulum Mart. ex DC (syn. P. persoonii McVaugh) (Myrtaceae) antimalarial decoction from the Wayana Amerindians.J Ethnopharmacol2016 Jul 127132714
Characterization, antioxidative and ACE inhibitory properties of hydrolysatesobtained from thornback ray (Raja clavata) muscle.J Proteomics2015 Oct 1425979167
Increased glyceraldehyde-3-phosphate dehydrogenase expression indicates highersurvival rates in male patients with hepatitis B virus-accociated hepatocellular carcinoma and cirrhosis.Exp Ther Med2015 May26136865
(1)H-NMR analysis of the human urinary metabolome in response to an 18-monthmulti-component exercise program and calcium-vitamin-D3 supplementation in older men.Appl Physiol Nutr Metab2014 Nov25198310
Genotoxicity of titanium dioxide nanoparticles.J Food Drug Anal2014 Mar24673907
ATPase inhibitor based luciferase assay for prolonged and enhanced ATP poolmeasurement as an efficient fish freshness indicator.Anal Bioanal Chem2014 Jul24838490
The effect of chilled conditioning at 4°C on selected water and lipid-solubleflavor precursors in Bison bison longissimus dorsi muscle and their impact onsensory characteristics.Meat Sci2014 Jan23896147
An ultra-sensitive monoclonal antibody-based competitive enzyme immunoassay for sterigmatocystin in cereal and oil products.PLoS One201425184275
Arxula adeninivorans xanthine oxidoreductase and its application in theproduction of food with low purine content.J Appl Microbiol2013 Sep23773263
An amperometric hypoxanthine biosensor based on Au@FeNPs for determination ofhypoxanthine in meat samples.Int J Biol Macromol2013 Nov24140402
Post-slaughter changes in ATP metabolites, reducing and phosphorylated sugars in chicken meat.Meat Sci2013 May23376434
Detection of in vivo mutation in the Hprt and Pig-a genes of rat lymphocytes.Methods Mol Biol201323896872
Metabolic engineering of the purine biosynthetic pathway in Corynebacteriumglutamicum results in increased intracellular pool sizes of IMP and hypoxanthine.Microb Cell Fact2012 Oct 2423092390
Alternaria toxins: Altertoxin II is a much stronger mutagen and DNA strand breaking mycotoxin than alternariol and its methyl ether in cultured mammalian cells.Toxicol Lett2012 Oct 222902351
Major furocoumarins in grapefruit juice II: phototoxicity, photogenotoxicity, and inhibitory potency vs. cytochrome P450 3A4 activity.Food Chem Toxicol2012 Mar22155270

Targets

General Function:
Purine-nucleoside phosphorylase activity
Specific Function:
The purine nucleoside phosphorylases catalyze the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
Gene Name:
PNP
Uniprot ID:
P00491
Molecular Weight:
32117.69 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [17139284 ]
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 ]
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 ]
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 ]