Uric acid

Identification

Generic Name
Uric acid
DrugBank Accession Number
DB08844
Background

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.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 168.1103
Monoisotopic: 168.028340014
Chemical Formula
C5H4N4O3
Synonyms
  • 2,6,8-trihydroxypurine
  • 2,6,8-trioxopurine
  • 2,6,8-trioxypurine
  • 7,9-dihydro-1H-purine-2,6,8(3H)-trione
  • Lithic acid
  • Purine-2,6,8(1H,3H,9H)-trione
  • Urate
  • Uricum acidum

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.

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Contraindications & Blackbox Warnings
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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 AvailableHumans
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

Adverse Effects
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Toxicity

Not Available

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe therapeutic efficacy of 1,2-Benzodiazepine can be decreased when used in combination with Uric acid.
AcebutololThe risk or severity of adverse effects can be increased when Acebutolol is combined with Uric acid.
AcetazolamideAcetazolamide may increase the excretion rate of Uric acid which could result in a lower serum level and potentially a reduction in efficacy.
AdalimumabThe serum concentration of Uric acid can be decreased when it is combined with Adalimumab.
AdenosineThe therapeutic efficacy of Adenosine can be decreased when used in combination with Uric acid.
Food Interactions
Not Available

Categories

Drug Categories
Chemical TaxonomyProvided by Classyfire
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
6-oxopurine / Alkaloid or derivatives / Aromatic heteropolycyclic compound / Azacycle / Azole / Heteroaromatic compound / Hydrocarbon derivative / Imidazole / Lactam / Organic nitrogen compound
show 11 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
uric acid (CHEBI:17775)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
268B43MJ25
CAS number
69-93-2
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

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. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
Human Metabolome Database
HMDB0000289
KEGG Compound
C00366
PubChem Compound
1175
PubChem Substance
175427118
ChemSpider
1142
BindingDB
50325824
RxNav
1427088
ChEBI
17775
ChEMBL
CHEMBL792
ZINC
ZINC000002041003
PDBe Ligand
URC
Wikipedia
Uric_acid
PDB Entries
1l5s / 2e3t / 2yzb / 3amz / 3an1 / 3bjp / 3l9g / 3rp7 / 4d12 / 4d17
show 16 more
MSDS
Download (27.4 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4RecruitingTreatmentHematopoietic and Lymphoid System Neoplasm / Malignant Solid Neoplasms / Tumour lysis syndrome1
4Unknown StatusPreventionHypouricemia, Renal / Urolithiasis1
4Unknown StatusPreventionKidney Diseases / Urological Diseases1
3CompletedPreventionHyperuricemia1
2, 3CompletedTreatmentAcute Ischemic Stroke1

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
logP-1.5Chemaxon
pKa (Strongest Acidic)7.25Chemaxon
pKa (Strongest Basic)-6.5Chemaxon
Physiological Charge-1Chemaxon
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-MSsplash10-00os-4900000000-54b6de73b60ab2faad65
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
MS/MS Spectrum - , negativeLC-MS/MSsplash10-01c0-3900000000-b3b3f0a20aaac71095d7
LC-MS/MS Spectrum - LC-ESI-IT , positiveLC-MS/MSsplash10-0f6x-0900000000-a6699ab18f69b21b3823
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-d08cf73afd1b4e228a9b
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-97d5c0c440fccd321d07
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014j-2900000000-a94046b86aa5272ba2b0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000l-4900000000-162b04ec5a8d236bd103
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-01c3-9000000000-b5790f35732ea571b823
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9000000000-eff454d25908b4b2d160
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-caa08c33e38fb54b99be
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-014i-0900000000-ae42bd6f3e935fc1d85d
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-014i-2900000000-2053fab587d5034a98d9
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0005-9300000000-8a892f30bba61c23c0b5
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-002b-9200000000-0e880880b8293e75cd6d
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0007-9000000000-befeeab377c9a1ab54cd
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-134.2688265
predicted
DarkChem Lite v0.1.0
[M-H]-134.4604265
predicted
DarkChem Lite v0.1.0
[M-H]-134.2938265
predicted
DarkChem Lite v0.1.0
[M-H]-134.2359265
predicted
DarkChem Lite v0.1.0
[M-H]-132.50656
predicted
DeepCCS 1.0 (2019)
[M-H]-134.2688265
predicted
DarkChem Lite v0.1.0
[M-H]-134.4604265
predicted
DarkChem Lite v0.1.0
[M-H]-134.2938265
predicted
DarkChem Lite v0.1.0
[M-H]-134.2359265
predicted
DarkChem Lite v0.1.0
[M-H]-132.50656
predicted
DeepCCS 1.0 (2019)
[M+H]+135.5988265
predicted
DarkChem Lite v0.1.0
[M+H]+135.4407265
predicted
DarkChem Lite v0.1.0
[M+H]+135.6571265
predicted
DarkChem Lite v0.1.0
[M+H]+135.6162265
predicted
DarkChem Lite v0.1.0
[M+H]+135.06227
predicted
DeepCCS 1.0 (2019)
[M+H]+135.5988265
predicted
DarkChem Lite v0.1.0
[M+H]+135.4407265
predicted
DarkChem Lite v0.1.0
[M+H]+135.6571265
predicted
DarkChem Lite v0.1.0
[M+H]+135.6162265
predicted
DarkChem Lite v0.1.0
[M+H]+135.06227
predicted
DeepCCS 1.0 (2019)
[M+Na]+135.3872265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.5839265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.5190265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.3077265
predicted
DarkChem Lite v0.1.0
[M+Na]+143.71794
predicted
DeepCCS 1.0 (2019)
[M+Na]+135.3872265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.5839265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.5190265
predicted
DarkChem Lite v0.1.0
[M+Na]+135.3077265
predicted
DarkChem Lite v0.1.0
[M+Na]+143.71794
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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. [Article]
  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. [Article]

Transporters

Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]
Kind
Protein
Organism
Humans
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. [Article]

Drug created at February 27, 2013 22:10 / Updated at June 12, 2020 16:52