Kynurenic acid, an intermediate uric acid channel, is absorbed by GPR35. In G qi/o chimeric G proteins, phosphoinositide synthesis and calcium stimulation are initiated through a GPR35-coupled mechanism by kynurenic acid. In GPR35-expressing cells, kynurenic acid increases [35S]guanosine 5'-O-(3-thiotriphosphate) binding; treatment with pertussis toxin eliminates this effect. GPR35 internalization is also induced by kynurenic acid [1]. Millimolar concentrations of the compounds were used to identify KYNA's neuromodulatory capabilities as well as the neuroprotective and anticonvulsant effects that go along with them. The other possibility is that KYNA functions as an internal kynurenate with a shallower closed curve and non-competitive localization against cultured hippocampi, as indicated by this and its effect on the clear ionotropic glutamate receptors responsible for these effects [NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and red algae alkaline salts]. These receptors have low affinity for each other, and the knowledge that KYNA concentrations in the brain are in the submicromolar range. The IC50 value of α7nAChRs on neurons is within the low micromolar range [2].

Mice peripheral blood leukocyte activity is influenced by kynurenic acid; the maximum concentration (250 mg/L) has the least effect, while the lowest concentration (2.5 mg/L) has the biggest effect. After giving acid to animals for seven and twenty-eight days, the smallest dose of kynurenic acid induced the ischemia response of T (p<0.05) [3].

Metabolism / Metabolites
Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces.

Toxicity Summary
Uremic toxins such as kynurenic acid are actively transported into the kidneys via organic ion transporters (especially OAT3). Increased levels of uremic toxins can stimulate the production of reactive oxygen species. This seems to be mediated by the direct binding or inhibition by uremic toxins of the enzyme NADPH oxidase (especially NOX4 which is abundant in the kidneys and heart) (A7868). Reactive oxygen species can induce several different DNA methyltransferases (DNMTs) which are involved in the silencing of a protein known as KLOTHO. KLOTHO has been identified as having important roles in anti-aging, mineral metabolism, and vitamin D metabolism. A number of studies have indicated that KLOTHO mRNA and protein levels are reduced during acute or chronic kidney diseases in response to high local levels of reactive oxygen species (A7869).

[1]. Wang J, et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem. 2006 Aug 4;281(31):22021-8.
[2]. Albuquerque EX, et al. Kynurenic acid as an antagonist of α7 nicotinic acetylcholine receptors in the brain: facts and challenges. Biochem Pharmacol. 2013 Apr 15;85(8):1027-32.
[3]. Małaczewska J, et al. Effect of oral administration of kynurenic acid on the activity of the peripheral blood leukocytes in mice. Cent Eur J Immunol. 2014;39(1):6-1

Kynurenic acid is a quinolinemonocarboxylic acid that is quinoline-2-carboxylic acid substituted by a hydroxy group at C-4. It has a role as a G-protein-coupled receptor agonist, a NMDA receptor antagonist, a nicotinic antagonist, a neuroprotective agent, a human metabolite and a Saccharomyces cerevisiae metabolite. It is a monohydroxyquinoline and a quinolinemonocarboxylic acid. It is a conjugate acid of a kynurenate.
Kynurenic Acid is under investigation in clinical trial NCT02340325 (FS2 Safety and Tolerability Study in Healthy Volunteers).
Kynurenic acid has been reported in Ephedra transitoria, Ephedra pachyclada, and other organisms with data available.
Kynurenic acid 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.
Kynurenic acid (KYNA) is a well-known endogenous antagonist of the glutamate ionotropic excitatory amino acid receptors N-methyl-D-aspartate (NMDA), alphaamino-3-hydroxy-5-methylisoxazole-4-propionic acid and kainate receptors and of the nicotine cholinergic subtype alpha 7 receptors. KYNA neuroprotective and anticonvulsive activities have been demonstrated in animal models of neurodegenerative diseases. Because of KYNA's neuromodulatory character, its involvement has been speculatively linked to the pathogenesis of a number of neurological conditions including those in the ageing process. Different patterns of abnormalities in various stages of KYNA metabolism in the CNS have been reported in Alzheimer's disease, Parkinson's disease and Huntington's disease. In HIV-1-infected patients and in patients with Lyme neuroborreliosis a marked rise of KYNA metabolism was seen. In the ageing process KYNA metabolism in the CNS of rats shows a characteristic pattern of changes throughout the life span. A marked increase of the KYNA content in the CNS occurs before the birth, followed by a dramatic decline on the day of birth. A low activity was seen during ontogenesis, and a slow and progressive enhancement occurs during maturation and ageing. This remarkable profile of KYNA metabolism alterations in the mammalian brain has been suggested to result from the development of the organisation of neuronal connections and synaptic plasticity, development of receptor recognition sites, maturation and ageing. There is significant evidence that KYNA can improve cognition and memory, but it has also been demonstrated that it interferes with working memory. Impairment of cognitive function in various neurodegenerative disorders is accompanied by profound reduction and/or elevation of KYNA metabolism. The view that enhancement of CNS KYNA levels could underlie cognitive decline is supported by the increased KYNA metabolism in Alzheimer's disease, by the increased KYNA metabolism in down's syndrome and the enhancement of KYNA function during the early stage of Huntington's disease. Kynurenic acid is the only endogenous N-methyl-D-aspartate (NMDA) receptor antagonist identified up to now, that mediates glutamatergic hypofunction. Schizophrenia is a disorder of dopaminergic neurotransmission, but modulation of the dopaminergic system by glutamatergic neurotransmission seems to play a key role. Despite the NMDA receptor antagonism, kynurenic acid also blocks, in lower doses, the nicotinergic acetycholine receptor, i.e., increased kynurenic acid levels can explain psychotic symptoms and cognitive deterioration. Kynurenic acid levels are described to be higher in the cerebrospinal fluid (CSF) and in critical central nervous system (CNS) regions of schizophrenics as compared to controls. (A3279, A3280).
Kynurenic acid is a metabolite found in or produced by Saccharomyces cerevisiae.
A broad-spectrum excitatory amino acid antagonist used as a research tool.

C10H7NO3

189.17

189.042

492-27-3

Kynurenic acid-d5;350820-13-2;Kynurenic acid sodium;2439-02-3

3845

Light yellow to yellow solid powder

1.4±0.1 g/cm3

358.4±42.0 °C at 760 mmHg

275 °C (dec.)(lit.)

170.5±27.9 °C

0.0±0.8 mmHg at 25°C

1.639

2.28

2

4

1

14

309

0

O=C1C([H])=C(C(=O)O[H])N([H])C2=C([H])C([H])=C([H])C([H])=C21

HCZHHEIFKROPDY-UHFFFAOYSA-N

InChI=1S/C10H7NO3/c12-9-5-8(10(13)14)11-7-4-2-1-3-6(7)9/h1-5H,(H,11,12)(H,13,14)

4-oxo-1H-quinoline-2-carboxylic acid

Kynuronic acid; Kynurenic acid; Kynurenic acid

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

0.1 M NaOH : ~12.5 mg/mL (~66.08 mM)
DMSO : ~9 mg/mL (~47.58 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 1.25 mg/mL (6.61 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 1.25 mg/mL (6.61 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

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Solubility in Formulation 3: 33.33 mg/mL (176.19 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)