| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
Potent and specific antagonist of the glycine B (GlyB) co-agonist site of the NMDA receptor (IC50 = 0.56 μM) [2]
- No affinity for the α7 nicotinic acetylcholine receptor [2] - No pharmacologically-relevant binding to 50 other ion channels, receptors, and transporters [2] |
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| ln Vitro |
7-Cl-KYNA is a potent and specific antagonist at the GlyB site of the NMDA receptor, with an IC50 of 0.56 μM [2].
- In distinction to kynurenic acid, 7-Cl-KYNA does not have affinity for the α7 nicotinic acetylcholine receptor, nor does it exhibit pharmacologically-relevant binding to 50 other ion channels, receptors, and transporters [2]. - The compound is essentially inactive at the GlyB site of the NMDA receptor on its own (IC50 for the prodrug L-4-chlorokynurenine is ~150 μM) [2]. |
| ln Vivo |
Pretreated with 7-chlorokynurenic acid (10 nM), male Sprague-Dawley rats exhibit a marked delay in the development of the motor (17.7 ± 2.9 stimulations per day) and electroencephalographic (17.7 ± 2.9 stimulations per day) components of the epileptic response [3].
After neuraxial delivery (intrathecal), 7-Cl-KYNA has potent antinociceptive actions [2]. - Systemic delivery of 7-Cl-KYNA has poor central bioavailability [2]. - The antinociceptive, neuroprotective, anti-epileptic, and antidepressant effects of 4-Cl-KYN/7-Cl-KYNA are mediated by NMDA receptor inhibition [2]. |
| Enzyme Assay |
Measurement of 7-Cl-KYNA in tissue and blood: For measurement of 7-Cl-KYNA, a 50 μl aliquot of the original tissue homogenate was diluted (1:1, v/v) with HPLC mobile phase (50 mM sodium acetate buffer containing 0.25 M zinc acetate and 10% acetonitrile, pH 6.2). To assess levels of 7-Cl-KYNA in blood, an aliquot of the deproteinated plasma sample was diluted (1:100, v/v) in the same HPLC mobile phase. 7-Cl-KYNA was then determined in appropriate aliquots of the tissue and plasma extract by HPLC analysis. Samples were applied to a 3 μm reverse phase HR-80 C18 column. After elution at a flow rate of 1.0 ml/min, 7-Cl-KYNA was detected fluorimetrically using an excitation wavelength of 344 nm and an emission wavelength of 398 nm. 7-Cl-KYNA eluted with a retention time of 5-6 min [2].
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| Cell Assay |
Whole-cell patch-clamp recording from primary cultures of rat cortical neurons: Cortical neurons were prepared from 1-day-old neonatal rats and cultured for 1–4 weeks. Recordings were made using the whole-cell patch configuration with a List EPC-7 amplifier. Patch pipettes (resistance ≈4 MΩ) were filled with an intracellular solution containing 120 mM CsF, 10 mM CsCl, 10 mM EGTA, 10 mM Hepes, 0.5 mM CaCl₂, 4 mM NaCl (pH 7.25 with CsOH). The external solution contained 139 mM NaCl, 2 mM KCl, 1.25 mM KH₂PO₄, 2 mM CaCl₂, 10 mM Hepes, 11 mM D-glucose, 0.1 μM tetrodotoxin (pH 7.4). Rapid solution changes were performed using a double-barreled micropipette. 7-chlorokynurenic acid (30 μM) was applied to cells before and during N-Me-D-Asp (30 μM) application (with or without added glycine). The inhibitory effect of 7-CI KYNA on N-Me-D-Asp-induced currents was assessed and reversibility tested by increasing glycine concentration. [1]
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| Animal Protocol |
Amygdala kindling model in rats: Male Sprague-Dawley rats (280–330 g) were anaesthetized with a halothane-N₂O mixture. A guide cannula and stainless steel bipolar electrode assembly were implanted into the right basolateral amygdala. After 7–10 days recovery, daily intra-amygdaloid microinjections (0.5 μl) were given using a 28-gauge stainless steel injection cannula. 7-chlorokynurenic acid was administered at a dose of 10 nmol per injection, either alone or co-injected with glycine (40 nmol). The vehicle was 50 mM phosphate buffer (pH 7.4). On Day 1, afterdischarge threshold (ADT) was estimated using an ascending limits method: 20 min after injection, an initial constant current stimulus of 100 μA (1 s train of 1 ms biphasic square-wave pulses at 60 Hz) was applied, and the stimulus intensity was increased by 25 μA every 2 min until an afterdischarge of at least 6 s was evoked. Thereafter, animals were stimulated daily at 30 min post-injection using 125% of their estimated threshold current. The duration of evoked afterdischarges and the severity of motor seizures (scored 0–5) were recorded. Daily stimulation continued until all control animals showed three consecutive Stage 5 seizures. 7-CI KYNA-treated animals received five additional daily stimulations after that point, then drug injections ceased and stimulations continued until fully kindled. Finally, animals were perfused transcardially with 10% formaldehyde in 0.9% saline, brains removed, sectioned, and stained with Cresyl violet to verify electrode/cannula placement. [3]
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| ADME/Pharmacokinetics |
Central Bioavailability: 7-Cl-KYNA has poor central bioavailability after systemic delivery [2].
- Brain and Spinal Cord Levels After Prodrug Administration: Following intraperitoneal (IP) injection of the prodrug L-4-chlorokynurenine (4-Cl-KYN) at doses of 167 mg/kg and 500 mg/kg, significant levels of the active metabolite (7-Cl-KYNA) were recovered in the brain and spinal cord (0.15-1.3 μM), i.e., concentrations close to or above its IC50 (0.56 μM) at the GlyB site. These levels were observed as soon as 30 min after administration of the prodrug [2]. - Serum Levels After Prodrug Administration: Following IP injection of 4-Cl-KYN at doses of 167 mg/kg and 500 mg/kg, levels of 7-Cl-KYNA in serum were up to 100 μM [2]. - Tissue Ratio: The ratio of 7-Cl-KYNA to 4-Cl-KYN was skewed toward the formation of 7-Cl-KYNA in spinal cord and serum (each ~1:10 on average) compared to the brain (~1:50 on average) [2]. |
| Toxicity/Toxicokinetics |
No signs of gross behavioral changes were observed in any control or drug-treated animals at any time during the amygdala kindling experiment (daily intra-amygdaloid injections of 10 nmol 7-chlorokynurenic acid for up to 20 days). [3]
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| References |
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| Additional Infomation |
7-Chlorokynuric acid is a quinoline monocarboxylic acid, consisting of quinoline acid with a hydroxyl group at position 4 and a chlorine group at position 7. It is a potent NMDA glutamate receptor antagonist, antagonizing the glycine binding site on NMDA receptors that is insensitive to strychnine. It can also prevent neurodegeneration induced by quinoline acid. It possesses neuroprotective and NMDA receptor antagonistic effects. It is an organochlorine compound and a quinoline monocarboxylic acid.
7-Chlorokynuric acid has been reported to exist in Streptomyces, and relevant data are available for reference. Mechanism of Action: 7-Cl-KYNA is an active metabolite produced in the brain. The prodrug L-4-chlorokynurenine (4-Cl-KYN) is actively transported into the CNS via the large neutral amino acid transporter. In astrocytes, kynurenine aminotransferases (KATs) catalyze its irreversible conversion to 7-Cl-KYNA, which then acts as a potent and selective antagonist of the GlyB site of the NMDA receptor to down-regulate NMDA receptor function [2]. - Potential Additional Mechanism: 4-Cl-KYN is also metabolized to 4-chloro-3-hydroxyanthranilic acid, a potent, selective inhibitor of 3-hydroxyanthranilic acid oxygenase (IC50: ~6 nM), the immediate biosynthetic enzyme of the excitotoxic NMDA receptor agonist quinolinic acid (QUIN). This may play a role in antinociceptive effects seen in pain models associated with inflammation-related QUIN accumulation in the spinal cord [2]. |
| Molecular Formula |
C10H6CLNO3
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|---|---|
| Molecular Weight |
223.61
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| Exact Mass |
223.004
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| CAS # |
18000-24-3
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| Related CAS # |
7-Chlorokynurenic acid sodium salt;1263094-00-3
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| PubChem CID |
1884
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| Appearance |
White to off-white solid powder
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| Density |
1.549 g/cm3
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| Boiling Point |
395ºC at 760 mmHg
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| Flash Point |
192.7ºC
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| Vapour Pressure |
6E-07mmHg at 25°C
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| Index of Refraction |
1.648
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| LogP |
2.292
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
15
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| Complexity |
340
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UAWVRVFHMOSAPU-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C10H6ClNO3/c11-5-1-2-6-7(3-5)12-8(10(14)15)4-9(6)13/h1-4H,(H,12,13)(H,14,15)
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| Chemical Name |
7-Chloro-4-hydroxyquinoline-2-carboxylic acid
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| Synonyms |
7CKA 7 CKA7-CKA 7-CTKA 7 CTKA7CTKA NSC 149792 NSC-149792NSC149792 7-Chlorokynurenic Acid 7 Chlorokynurenic Acid7-chloro KYNA 7 chloro KYNA
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~16.67 mg/mL (~74.55 mM)
H2O : ~1 mg/mL (~4.47 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (7.47 mM) (saturation unknown) in 10% DMSO + 40% PEG300 +5% Tween-80 + 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 16.7 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4721 mL | 22.3604 mL | 44.7207 mL | |
| 5 mM | 0.8944 mL | 4.4721 mL | 8.9441 mL | |
| 10 mM | 0.4472 mL | 2.2360 mL | 4.4721 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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