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 often accumulate in the blood due to overeating or poor kidney filtration. Most uremic toxins are metabolic waste products that are normally excreted through urine or feces.

Toxicity Summary
Uremic toxins, such as kynurenic acid, can be actively transported to the kidneys via organic ion transporters, particularly OAT3. Elevated uremic toxin levels can stimulate the production of reactive oxygen species (ROS). This appears to be mediated by the direct binding of uremic toxins to or inhibition of NADPH oxidases, particularly NOX4, which is abundant in the kidneys and heart (A7868). ROS can induce a variety of different DNA methyltransferases (DNMTs) involved in the silencing of a protein called KLOTHO. KLOTHO has been shown to play an important role in anti-aging, mineral metabolism, and vitamin D metabolism. Multiple studies have shown that in acute or chronic kidney disease, the mRNA and protein levels of KLOTHO are reduced due to elevated local ROS levels (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 quinoline monocarboxylic acid, specifically quinoline-2-carboxylic acid with a hydroxyl group substituted at the C-4 position. It has multiple functions, including acting as a G protein-coupled receptor agonist, NMDA receptor antagonist, nicotine receptor antagonist, neuroprotective agent, human metabolite, and a Saccharomyces cerevisiae metabolite. It is a monohydroxyquinoline and quinoline monocarboxylic acid, and is also the conjugate acid of Kynurenic acid. Kynurenic acid is currently being investigated in the clinical trial NCT02340325 (FS2 Safety and Tolerability Study in Healthy Volunteers). Kynurenic acid has been reported to be present in ephedra, Ephedra sinica, and other organisms with relevant data. Kynurenic acid is a uremic toxin. Based on chemical and physical properties, uremic toxins can be classified into three main categories: 1) small, water-soluble, non-protein-bound compounds, such as urea; 2) small, lipid-soluble and/or protein-bound compounds, such as phenols; and 3) larger, so-called medium-molecular-weight compounds, such as β2-microglobulin. Long-term exposure to uremic toxins can lead to various diseases, including kidney damage, chronic kidney disease, and cardiovascular disease. Kynuronic acid (KYNA) is a known antagonist of endogenous glutamate ionotropic excitatory amino acid receptors (such as N-methyl-D-aspartate (NMDA) receptors, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors, and phycocyanine receptors) and nicotinic cholinergic subtype α7 receptors. In animal models of neurodegenerative diseases, KYNA has been shown to possess neuroprotective and anticonvulsant activities. Due to its neuromodulatory properties, KYNA is hypothesized to be involved in the pathogenesis of various neurological diseases, including those related to aging. Abnormal patterns of KYNA metabolism at different stages in the central nervous system (CNS) have been reported in Alzheimer's disease, Parkinson's disease, and Huntington's disease. KYNA metabolism is significantly elevated in HIV-1 infected individuals and Lyme disease patients with neurological infections. During aging, KYNA metabolism in the rat CNS exhibits a characteristic pattern of changes throughout the lifespan. Prenatal KYNA levels are significantly elevated, followed by a sharp decline on the day of birth. Kynuronic acid (KYNA) exhibits low activity during individual development, slowly and gradually increasing during maturation and aging. This significant pattern of altered KYNA metabolism in the mammalian brain is thought to stem from tissue development of neuronal connections and synaptic plasticity, development of receptor recognition sites, and maturation and aging processes. There is substantial evidence that kynuronic acid can improve cognition and memory, but other studies suggest it can interfere with working memory. Cognitive impairment in various neurodegenerative diseases is accompanied by significant decreases and/or increases in KYNA metabolism. Increased KYNA metabolism in Alzheimer's disease and Down syndrome, as well as enhanced KYNA function in the early stages of Huntington's disease, support the idea that elevated central nervous system KYNA levels may be a potential mechanism for cognitive decline. Kynuronic acid is the only known endogenous N-methyl-D-aspartate (NMDA) receptor antagonist that mediates glutamatergic dysfunction. Schizophrenia is a dopaminergic neurotransmission disorder, but glutamatergic neurotransmission appears to play a crucial role in the regulation of the dopaminergic system. Although kynurenic acid has NMDA receptor antagonistic effects, low doses of kynurenic acid can also block nicotinic acetylcholine receptors, meaning that elevated kynurenic acid levels can explain psychotic symptoms and cognitive decline. Studies have shown that patients with schizophrenia have higher levels of kynurenic acid in the cerebrospinal fluid and key central nervous system regions compared to controls (A3279, A3280). Kynurenic acid is a metabolite of Saccharomyces cerevisiae, produced by or present in the yeast. It is a broad-spectrum excitatory amino acid antagonist and is frequently 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.

---

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.

---

View More

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.

---

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