You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameUric Acid
Accession NumberDB08844  (DB01696, EXPT03202)
TypeSmall Molecule
GroupsExperimental, Investigational
Description

Uric acid is the last product of purine metabolism in humans. The formation of uric acid is through the enzyme xanthine oxidase, which oxidizes oxypurines. Normally a small amount of uric acid is present in the body, but when there is an excess amount in the blood, called hyperuricemia, this can lead to gout and formation of kidney stones. As a therapeutic agent, it is known that uric acid is increased in response to oxidative stress, and as such, uric acid acts as an antioxidant. At present (August 2013), there is no approved formulation or indication for uric acid. In one country, Spain, uric acid is an investigational drug in a phase 3 trial studying its effects as an adjunct to alteplase in acute ischemic stroke.

Structure
Thumb
Synonyms
2,6,8-Trihydroxypurine
7,9-dihydro-1H-purine-2,6,8(3H)-trione
Urate
External Identifiers Not Available
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII268B43MJ25
CAS number69-93-2
WeightAverage: 168.1103
Monoisotopic: 168.028340014
Chemical FormulaC5H4N4O3
InChI KeyInChIKey=LEHOTFFKMJEONL-UHFFFAOYSA-N
InChI
InChI=1S/C5H4N4O3/c10-3-1-2(7-4(11)6-1)8-5(12)9-3/h(H4,6,7,8,9,10,11,12)
IUPAC Name
2,3,6,7,8,9-hexahydro-1H-purine-2,6,8-trione
SMILES
O=C1NC2=C(N1)C(=O)NC(=O)N2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as alkaloids and derivatives. These are naturally occurring chemical compounds that contain mostly basic nitrogen atoms. This group also includes some related compounds with neutral and even weakly acidic properties. Also some synthetic compounds of similar structure are attributed to alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen, sulfur and more rarely other elements such as chlorine, bromine, and phosphorus.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassNot Available
Sub ClassNot Available
Direct ParentAlkaloids and derivatives
Alternative Parents
Substituents
  • Alkaloid or derivatives
  • Xanthine
  • Purinone
  • 6-oxopurine
  • Purine
  • Imidazopyrimidine
  • Pyrimidone
  • Pyrimidine
  • Heteroaromatic compound
  • Vinylogous amide
  • Imidazole
  • Azole
  • Urea
  • Lactam
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationAt present (August 2013), there is no approved indication for uric acid. The potential therapeutic use for uric acid is as an adjunct in acute ischemic stroke.
PharmacodynamicsUric acid is a strong reducing agent (donates electrons) and an antioxidant. Normally in humans, one of the main antioxidants in plasma is uric acid. Several animal studies have found that animals given exogenous uric acid within 3 hours after a stroke had decreased infarct volume, improved neurologic function, and diminished inflammatory responses providing evidence for the neuroprotective effects of uric acid. In some early human studies, uric acid has so far shown similar neuroprotective effects, in both the cortex and subcortex areas, due to its antioxidant effects such as decreased lipid peroxidation, and there appears to be no significant toxicities.
Mechanism of actionThe exact mechanism of action for uric acid's antioxidant effects have not yet been elucidated.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

In higher primates and humans, the enzyme, uricase, is absent, and thus uric acid is not further metabolized and is excreted. In all other mammals, uric acid is metabolized by uricase to allantoin, which is then excreted.

Route of eliminationUric acid is eliminated by the kidneys.
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal AbsorptionNot AvailableNot Available
Blood Brain BarrierNot AvailableNot Available
Caco-2 permeableNot AvailableNot Available
P-glycoprotein substrateNot AvailableNot Available
P-glycoprotein inhibitor INot AvailableNot Available
P-glycoprotein inhibitor IINot AvailableNot Available
Renal organic cation transporterNot AvailableNot Available
CYP450 2C9 substrateNot AvailableNot Available
CYP450 2D6 substrateNot AvailableNot Available
CYP450 3A4 substrateNot AvailableNot Available
CYP450 1A2 substrateNot AvailableNot Available
CYP450 2C9 inhibitorNot AvailableNot Available
CYP450 2D6 inhibitorNot AvailableNot Available
CYP450 2C19 inhibitorNot AvailableNot Available
CYP450 3A4 inhibitorNot AvailableNot Available
CYP450 inhibitory promiscuityNot AvailableNot Available
Ames testNot AvailableNot Available
CarcinogenicityNot AvailableNot Available
BiodegradationNot AvailableNot Available
Rat acute toxicityNot AvailableNot applicable
hERG inhibition (predictor I)Not AvailableNot Available
hERG inhibition (predictor II)Not AvailableNot Available
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting pointGreater than 300 °CFrom MSDS.
water solubility60 mg/L (at 20 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-2.17NAHUM,A & HORVATH,C (1980)
pKa5.4KORTUM,G ET AL (1961)
Predicted Properties
PropertyValueSource
Water Solubility1.76 mg/mLALOGPS
logP-1.1ALOGPS
logP-1.5ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)7.61ChemAxon
pKa (Strongest Basic)-6.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count4ChemAxon
Polar Surface Area99.33 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity45.63 m3·mol-1ChemAxon
Polarizability13.61 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
GC-MSGC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)splash10-0537-0913400000-bd24364053510c462adeView in MoNA
GC-MSGC-MS Spectrum - GC-MS (4 TMS)splash10-052f-0603900000-8c1224738bed2608c262View in MoNA
GC-MSGC-MS Spectrum - GC-MS (3 TMS)splash10-0g59-5917000000-4b28946431495667844bView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)splash10-014i-0900000000-0525c12dc3951f55a2c8View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)splash10-006w-9500000000-fe10d491ad634ca46332View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)splash10-0gbd-9100000000-d48a3e7919c385949313View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0900000000-971b5c8c5d975d306fedView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-016r-1900000000-72edb3607fe9beb9b805View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0zgi-9500000000-753be769a0b48fc2960bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0900000000-a4f5b18495486c5a1d5aView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01b9-1900000000-bc9e45f168dafb0d874cView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9100000000-e01e386869d687364c61View in MoNA
MSMass Spectrum (Electron Ionization)splash10-002f-9200000000-e5abb655836214cc56b3View in MoNA
References
Synthesis Reference

Brenner-Holzach, O.; Leuthardt, F. Uric acid formation from glucose carbon in Drosophila melanogaster. Preliminary report. Helvetica Chimica Acta (1963), 46(4), 1426-8.

General References
  1. Chamorro A, Planas AM, Muner DS, Deulofeu R: Uric acid administration for neuroprotection in patients with acute brain ischemia. Med Hypotheses. 2004;62(2):173-6. [PubMed:14962621 ]
  2. Romanos E, Planas AM, Amaro S, Chamorro A: Uric acid reduces brain damage and improves the benefits of rt-PA in a rat model of thromboembolic stroke. J Cereb Blood Flow Metab. 2007 Jan;27(1):14-20. Epub 2006 Apr 5. [PubMed:16596120 ]
  3. Amaro S, Soy D, Obach V, Cervera A, Planas AM, Chamorro A: A pilot study of dual treatment with recombinant tissue plasminogen activator and uric acid in acute ischemic stroke. Stroke. 2007 Jul;38(7):2173-5. Epub 2007 May 24. [PubMed:17525395 ]
  4. Maxwell SR, Thomason H, Sandler D, Leguen C, Baxter MA, Thorpe GH, Jones AF, Barnett AH: Antioxidant status in patients with uncomplicated insulin-dependent and non-insulin-dependent diabetes mellitus. Eur J Clin Invest. 1997 Jun;27(6):484-90. [PubMed:9229228 ]
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB Entries
FDA labelNot Available
MSDSDownload (27.4 KB)
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Vitamin binding
Specific Function:
Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
Gene Name:
PYGL
Uniprot ID:
P06737
Molecular Weight:
97147.82 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. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. [PubMed:9228014 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. Cha SH, Sekine T, Fukushima JI, Kanai Y, Kobayashi Y, Goya T, Endou H: Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney. Mol Pharmacol. 2001 May;59(5):1277-86. [PubMed:11306713 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Sugar:proton symporter activity
Specific Function:
Transport urate and fructose. May have a role in the urate reabsorption by proximal tubules. Also transports glucose at low rate.
Gene Name:
SLC2A9
Uniprot ID:
Q9NRM0
Molecular Weight:
58701.205 Da
References
  1. Vitart V, Rudan I, Hayward C, Gray NK, Floyd J, Palmer CN, Knott SA, Kolcic I, Polasek O, Graessler J, Wilson JF, Marinaki A, Riches PL, Shu X, Janicijevic B, Smolej-Narancic N, Gorgoni B, Morgan J, Campbell S, Biloglav Z, Barac-Lauc L, Pericic M, Klaric IM, Zgaga L, Skaric-Juric T, Wild SH, Richardson WA, Hohenstein P, Kimber CH, Tenesa A, Donnelly LA, Fairbanks LD, Aringer M, McKeigue PM, Ralston SH, Morris AD, Rudan P, Hastie ND, Campbell H, Wright AF: SLC2A9 is a newly identified urate transporter influencing serum urate concentration, urate excretion and gout. Nat Genet. 2008 Apr;40(4):437-42. doi: 10.1038/ng.106. Epub 2008 Mar 9. [PubMed:18327257 ]
Comments
comments powered by Disqus
Drug created on February 27, 2013 15:10 / Updated on April 07, 2016 11:43