Identification

Name
Uric Acid
Accession Number
DB08844  (DB01696, EXPT03202)
Type
Small Molecule
Groups
Experimental, 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
Categories
UNII
268B43MJ25
CAS number
69-93-2
Weight
Average: 168.1103
Monoisotopic: 168.028340014
Chemical Formula
C5H4N4O3
InChI Key
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

Pharmacology

Indication

At 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.

Structured Indications
Not Available
Pharmacodynamics

Uric 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 action

The exact mechanism of action for uric acid's antioxidant effects have not yet been elucidated.

TargetActionsOrganism
UGlycogen phosphorylase, liver formNot AvailableHuman
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not 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 elimination

Uric acid is eliminated by the kidneys.

Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

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
Human Metabolome Database
HMDB00289
KEGG Compound
C00366
PubChem Compound
1175
PubChem Substance
175427118
ChemSpider
1142
BindingDB
50325824
ChEBI
17775
ChEMBL
CHEMBL792
HET
URC
Wikipedia
Uric_acid
PDB Entries
1l5s / 2e3t / 2yzb / 3amz / 3an1 / 3bjp / 3l9g / 3obp / 3rp7 / 4d12
show 9 more
MSDS
Download (27.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedOtherHealthy Volunteers1
2, 3CompletedTreatmentAcute Ischemic Stroke (AIS)1
Not AvailableCompletedScreeningOther Diseases or Conditions1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)Greater 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 FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-EI-TOF (Pegasus III TOF-MS system, Leco; GC 6890, Agilent Technologies)GC-MSsplash10-0537-0913400000-bd24364053510c462ade
GC-MS Spectrum - GC-MS (4 TMS)GC-MSsplash10-052f-0603900000-8c1224738bed2608c262
GC-MS Spectrum - GC-MS (3 TMS)GC-MSsplash10-0g59-5917000000-4b28946431495667844b
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-0537-0913400000-bd24364053510c462ade
GC-MS Spectrum - GC-MSGC-MSsplash10-052f-0603900000-8c1224738bed2608c262
GC-MS Spectrum - GC-MSGC-MSsplash10-0g59-5917000000-4b28946431495667844b
GC-MS Spectrum - GC-EI-TOFGC-MSsplash10-052g-0902500000-05851611f4bbf0745b81
Mass Spectrum (Electron Ionization)MSsplash10-002f-9200000000-e5abb655836214cc56b3
MS/MS Spectrum - Quattro_QQQ 10V, Positive (Annotated)LC-MS/MSsplash10-014i-0900000000-0525c12dc3951f55a2c8
MS/MS Spectrum - Quattro_QQQ 25V, Positive (Annotated)LC-MS/MSsplash10-006w-9500000000-fe10d491ad634ca46332
MS/MS Spectrum - Quattro_QQQ 40V, Positive (Annotated)LC-MS/MSsplash10-0gbd-9100000000-d48a3e7919c385949313
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-971b5c8c5d975d306fed
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-016r-1900000000-72edb3607fe9beb9b805
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0zgi-9500000000-753be769a0b48fc2960b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-a4f5b18495486c5a1d5a
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01b9-1900000000-bc9e45f168dafb0d874c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9100000000-e01e386869d687364c61
MS/MS Spectrum - , negativeLC-MS/MSsplash10-01c0-3900000000-b3b3f0a20aaac71095d7
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0f6x-0900000000-a6699ab18f69b21b3823
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as xanthines. These are purine derivatives with a ketone group conjugated at carbons 2 and 6 of the purine moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Imidazopyrimidines
Sub Class
Purines and purine derivatives
Direct Parent
Xanthines
Alternative Parents
6-oxopurines / Alkaloids and derivatives / Pyrimidones / Vinylogous amides / Imidazoles / Heteroaromatic compounds / Ureas / Lactams / Azacyclic compounds / Organopnictogen compounds
show 4 more
Substituents
Xanthine / 6-oxopurine / Purinone / Alkaloid or derivatives / Pyrimidone / Pyrimidine / Azole / Imidazole / Heteroaromatic compound / Vinylogous amide
show 11 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
uric acid (CHEBI:17775)

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 ...
Gene Name
PYGL
Uniprot ID
P06737
Uniprot Name
Glycogen phosphorylase, liver form
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 ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
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, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
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
Uniprot Name
Solute carrier family 2, facilitated glucose transporter member 9
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]

Drug created on February 27, 2013 15:10 / Updated on November 09, 2017 04:41