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
Structure for Uric acid (DB08844)
- 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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Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.- 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.
Target Actions Organism UGlycogen phosphorylase, liver form Not Available Humans - 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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.- 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.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The therapeutic efficacy of 1,2-Benzodiazepine can be decreased when used in combination with Uric acid. Acebutolol The risk or severity of adverse effects can be increased when Acebutolol is combined with Uric acid. Acetazolamide Acetazolamide may increase the excretion rate of Uric acid which could result in a lower serum level and potentially a reduction in efficacy. Adalimumab The serum concentration of Uric acid can be decreased when it is combined with Adalimumab. Adenosine The therapeutic efficacy of Adenosine can be decreased when used in combination with Uric acid. Allopurinol The serum concentration of Uric acid can be increased when it is combined with Allopurinol. Alprazolam The therapeutic efficacy of Alprazolam can be decreased when used in combination with Uric acid. Amiodarone The serum concentration of Uric acid can be increased when it is combined with Amiodarone. Amobarbital The serum concentration of Uric acid can be decreased when it is combined with Amobarbital. Amphetamine The risk or severity of adverse effects can be increased when Amphetamine is combined with Uric acid. 
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- 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
- 9H-purine-2,6,8-triol
- 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
- 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]
- 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]
- 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]
- 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]
- External Links
- PDB Entries
- 1l5s / 2e3t / 2yzb / 3amz / 3an1 / 3bjp / 3l9g / 3obp / 3rp7 / 4d12 … show 16 more
- MSDS
- Download (27.4 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Recruiting Treatment Hematopoietic and Lymphoid Cell Neoplasm / Malignant Solid Neoplasms / Tumour lysis syndrome 1 4 Unknown Status Prevention Hypouricemia, Renal / Urolithiasis 1 4 Unknown Status Prevention Kidney Diseases / Urological Diseases 1 3 Completed Prevention Hyperuricemia 1 2, 3 Completed Treatment Acute Ischemic Stroke 1 1 Completed Other Healthy Subjects (HS) 1 Not Available Completed Not Available Uric Acid Serum 1 Not Available Completed Other Hyperuricemia / Obesity / Syndrome, Metabolic 1 Not Available Completed Screening Other Diseases or Conditions 1 Not Available Completed Treatment Rheumatoid Arthritis 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) Greater than 300 °C From MSDS. water solubility 60 mg/L (at 20 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992) logP -2.17 NAHUM,A & HORVATH,C (1980) pKa 5.4 KORTUM,G ET AL (1961) - Predicted Properties
Property Value Source Water Solubility 9.61 mg/mL ALOGPS logP -0.41 ALOGPS logP 0.75 Chemaxon logS -1.2 ALOGPS pKa (Strongest Acidic) 8.17 Chemaxon pKa (Strongest Basic) -1.8 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 4 Chemaxon Polar Surface Area 115.15 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 37.26 m3·mol-1 Chemaxon Polarizability 14.1 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Targets
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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
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
- 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
- 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
- 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