D-Kynurenine
(Synonyms: 犬尿氨酸) 目录号 : GC45705
An antagonist of GPR109B
Cas No.:13441-51-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
D-Kynurenine is an antagonist of hydroxycarboxylic acid receptor 3 HCA3/GPR109B (EC50 = 2.61 μM in a luciferase reporter assay) and a metabolite of D-tryptophan.1 It increases levels of intracellular calcium and decreases forskolin-stimulated production of cAMP in CHO cells expressing human HCA3/GPR109B when used at concentrations of 10 and 100, or 1,000 μM, respectively. D-Kynurenine (10 μM) increases expression of vimentin and decreases expression of E-cadherin in 95D lung cancer cells.2 It has been used as a substrate in fluorometric assays for D-amino acid oxidase activity.3,4
|1. Irukayama-Tomobe, Y., Tanaka, H., Yokomizo, T., et al. Aromatic D-amino acids act as chemoattractant factors for human leukocytes through a G protein-coupled receptor, GPR109B. Proc. Natl. Acad. Sci. USA 106(10), 3930-3934 (2009).|2. Duan, Z., Li, Y., and Li, L. Promoting epithelial-to-mesenchymal transition by D-kynurenine via activating aryl hydrocarbon receptor. Mol. Cell. Biochem. 448(1-2), 165-173 (2018).|3. Kozaki, A., Iwasa, S., Hosoda, S., et al. Fluorimetric assay for D-amino acid oxidase activity in rat brain homogenate by using D-kynurenine as a substrate. Biosci. Trends 6(5), 241-247 (2012).|4. Song, Z., Ogaya, T., Ishii, K., et al. Utilization of kynurenic acid produced from D-kynurenine in an in vitro assay of D-amino acid oxidase activity. J. Health Sci. 56(3), 341-346 (2010).
| Cas No. | 13441-51-5 | SDF | |
| 别名 | 犬尿氨酸 | ||
| Canonical SMILES | NC1=C(C(C[C@@H](N)C(O)=O)=O)C=CC=C1 | ||
| 分子式 | C10H12N2O3 | 分子量 | 208.2 |
| 溶解度 | 0.5M HCl: 50 mg/ml | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 4.8031 mL | 24.0154 mL | 48.0307 mL |
| 5 mM | 0.9606 mL | 4.8031 mL | 9.6061 mL |
| 10 mM | 0.4803 mL | 2.4015 mL | 4.8031 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Direct Fluorescence Evaluation of d-Amino Acid Oxidase Activity Using a Synthetic D-Kynurenine Derivative
Anal Chem 2022 Oct 25;94(42):14530-14536.PMID:36222234DOI:10.1021/acs.analchem.2c00775.
d-Amino acid oxidase (DAO) has been suggested to be associated with the central nervous system diseases, such as schizophrenia. We newly synthesized a nonfluorescent 5-methylthio-d-kynurenine (MeS-d-KYN), which was converted to blue-fluorescent 6-MeS-kynurenic acid (MeS-KYNA, λex = 364 nm, λem = 450 nm) through a one-step reaction by incubation with DAO. It was revealed that fluorescence intensity increased accompanied by commercial porcine kidney DAO activity (unit) with a good correlation (R2 = 0.9972), suggesting that the fluorometric evaluation of DAO activity using MeS-d-KYN is feasible. MeS-d-KYN was applied to fluorescent DAO imaging in cultured LLC-PK1 cells, and the blue fluorescence of MeS-KYNA overlapped considerably with the location of peroxisomes, which was suggested to be the location of DAO in the cells. Because fluorescence was diminished in the presence of 6-chloro-1,2-benzisoxazol-3(2H)-one (CBIO), a DAO inhibitor, it was considered that DAO activity in cells could be directly evaluated using MeS-d-KYN as the substrate.
A method for the determination of D-Kynurenine in biological tissues
Anal Bioanal Chem 2013 Dec;405(30):9747-54.PMID:24158577DOI:10.1007/s00216-013-7399-7.
D-Kynurenine (D-KYN), a metabolite of D-tryptophan, can serve as the bioprecursor of kynurenic acid (KYNA) and 3-hydroxykynurenine, two neuroactive compounds that are believed to play a role in the pathophysiology of several neurological and psychiatric diseases. In order to investigate the possible presence of D-KYN in biological tissues, we developed a novel assay based on the conversion of D-KYN to KYNA by purified D-amino acid oxidase (D-AAO). Samples were incubated with D-AAO under optimal conditions for measuring D-AAO activity (100 mM borate buffer, pH 9.0), and newly produced KYNA was detected by high-performance liquid chromatography (HPLC) with fluorimetric detection. The detection limit for D-KYN was 300 fmol, and linearity of the assay was ascertained up to 300 pmol. No assay interference was noted when other D-amino acids, including D-serine and D-aspartate, were present in the incubation mixture at 50-fold higher concentrations than D-KYN. Using this new method, D-KYN was readily detected in the brain, liver, and plasma of mice treated systemically with D-KYN (300 mg/kg). In these experiments, enantioselectivity was confirmed by determining total kynurenine levels in the same samples using a conventional HPLC assay. Availability of a sensitive, specific, and simple method for D-KYN measurement will be instrumental for evaluating whether D-KYN should be considered for a role in physiology and pathology.
Promoting epithelial-to-mesenchymal transition by D-Kynurenine via activating aryl hydrocarbon receptor
Mol Cell Biochem 2018 Nov;448(1-2):165-173.PMID:29442266DOI:10.1007/s11010-018-3323-y.
Epithelial-to-mesenchymal transition (EMT) is believed to play key roles in the process of cancer metastasis. The molecular changes during EMT are characterized by the down-regulation of epithelial proteins, such as E-cadherin, and the up-regulation of mesenchymal proteins, such as vimentin (VIM). It has been demonstrated that L-kynurenine (L-Kyn), a physiological ligand of Aryl hydrocarbon receptor (Ahr), promotes cancer cells to metastasize. However, the effects of D-enantiomer of kynurenine, D-Kynurenine (D-Kyn), on metastasis are still unclear. In the present paper, we firstly confirmed that D-Kyn (10, 40, 60, and 100 µM) positively regulated the metastasis of 95D cells, a lung cancer cell line, which was reduced upon siRNAAhr treatment. Moreover, significant enhancement VIM expression was detected in the presence of D-Kyn (10 and 40 µM). In contrast, 10 µM D-Kyn markedly attenuated E-cadherin level. Additionally, 10 µM D-Kyn-mediated changes of VIM and E-cadherin were substantially attenuated on siRNAAhr treatment as well. Most importantly, the evidences-10/40 µM D-Kyn-induced up-regulation of CYP1A1, 10 µM D-Kyn-induced increase of nuclear transfer of Ahr, and 10/40/60/100 µM D-Kyn-induced enhancement of DER-luciferase activity-indicated that D-Kyn was capable of activating Ahr in fact. These results suggest that D-Kyn increases lung cancer cells to metastasize by activating Ahr.
Role of d-amino acid oxidase in the production of kynurenine pathway metabolites from d-tryptophan in mice
J Neurochem 2016 Feb;136(4):804-814.PMID:26661897DOI:10.1111/jnc.13455.
The kynurenine pathway (KP), the major catabolic route of the essential amino acid l-tryptophan (l-TRP), contains several neuroactive compounds, including kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN). The role of the d-enantiomer (d-TRP) in KP metabolism has received little attention so far. d-TRP can be converted to l-TRP by d-amino acid oxidase, and the same enzyme can produce D-Kynurenine, a known bioprecursor of KYNA. To analyze these complex metabolic events systematically in vivo, we injected mice with d-TRP (300 mg/kg, i.p.) and examined KP metabolism in the absence or presence of the d-amino acid oxidase inhibitor 3-methylpyrazole-5-carboxylic acid (MPC; 100 mg/kg, i.p.,). After 90 min, newly formed l-TRP was recovered in plasma, liver, forebrain, and cerebellum, and MPC prevented its neosynthesis in all tissues. In the same animals, de novo production of D-Kynurenine from d-TRP was also observed, but was much higher in the periphery than in the brain. d-TRP administration raised KYNA, 3-HK, and QUIN levels in all tissues examined, and KYNA production from d-TRP was significantly reduced after pre-treatment with MPC. These results indicate that catabolic routes other than those classically ascribed to l-TRP and l-kynurenine can account for the synthesis of KYNA, 3-HK and QUINin vivo. The essential amino acid l-tryptophan is catabolized via the kynurenine pathway (KP). We explored the role of the d-enantiomer in KP metabolism in mice in vivo. We report that d-tryptophan is metabolized in both brain and periphery and converted to KP metabolites, including D-Kynurenine and l-kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid. Pharmacological experiments confirm the involvement of d-amino acid oxidase in these processes. Our results indicate that this enzyme participates in the synthesis of KP metabolites from d-tryptophan.
Enzymatic transamination of D-Kynurenine generates kynurenic acid in rat and human brain
J Neurochem 2012 Mar;120(6):1026-35.PMID:22224417DOI:10.1111/j.1471-4159.2012.07653.x.
In the mammalian brain, the α7 nicotinic and NMDA receptor antagonist kynurenic acid is synthesized by irreversible enzymatic transamination of the tryptophan metabolite l-kynurenine. D-Kynurenine, too, serves as a bioprecursor of kynurenic acid in several organs including the brain, but the conversion is reportedly catalyzed through oxidative deamination by d-amino acid oxidase. Using brain and liver tissue homogenates from rats and humans, and conventional incubation conditions for kynurenine aminotransferases, we show here that kynurenic acid production from D-Kynurenine, like the more efficient kynurenic acid synthesis from l-kynurenine, is blocked by the aminotransferase inhibitor amino-oxyacetic acid. In vivo, focal application of 100 μM D-Kynurenine by reverse microdialysis led to a steady rise in extracellular kynurenic acid in the rat striatum, causing a 4-fold elevation after 2 h. Attesting to functional significance, this increase was accompanied by a 36% reduction in extracellular dopamine. Both of these effects were duplicated by perfusion of 2 μM l-kynurenine. Co-infusion of amino-oxyacetic acid (2 mM) significantly attenuated the in vivo effects of D-Kynurenine and essentially eliminated the effects of l-kynurenine. Thus, enzymatic transamination accounts in part for kynurenic acid synthesis from D-Kynurenine in the brain. These results are discussed with regard to implications for brain physiology and pathology.