Page last updated: 2024-12-04

kynurenine

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Description

L-kynurenine : A kynurenine that has L configuration. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Kynurenine: A metabolite of the essential amino acid tryptophan metabolized via the tryptophan-kynurenine pathway. [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

kynurenine : A ketone that is alanine in which one of the methyl hydrogens is substituted by a 2-aminobenzoyl group. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID161166
CHEMBL ID498416
CHEBI ID16946
SCHEMBL ID20875
MeSH IDM0012093
PubMed CID846
CHEMBL ID1377927
CHEBI ID28683
SCHEMBL ID20874
MeSH IDM0012093

Synonyms (137)

Synonym
(2s)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid
CHEBI:16946 ,
3-(2-aminobenzoyl)-l-alanine
kynurenine, l-
ccris 4425
kynurenin
2922-83-0
C00328
l-kynurenine
3-anthraniloyl-l-alanine
l-kynurenine, >=98% (hplc)
kyn ,
DB02070
NCGC00163345-01
K-9020
l-kynurenine, free base
ksc-11-228-1
KUC106759N
BMSE000172
3-anthraniloyl-alanine
K0016
CHEMBL498416
(2s)-2-amino-4-(2-aminophenyl)-4-oxo-butanoic acid;l-kynurenine
A819827
unii-02jw4j5r44
02jw4j5r44 ,
(s)-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid
S5839
(s)-kynurenine
l-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid
SCHEMBL20875
2-amino-4-(2-aminophenyl)-4-oxobutanoic acid #
quinurenine
kynurenine, (+)-
benzenebutanoic acid, .alpha.,2-diamino-.gamma.-oxo-, (s)-
tryptophan impurity c [ep impurity]
n-acetyltryptophan impurity c [ep impurity]
l-3-(o-aminobenzoyl)alanine
benzenebutanoic acid, .alpha.,2-diamino-.gamma.-oxo-, (.alpha.s)-
benzenebutanoic acid, alpha,2-diamino-gamma-oxo-, (alphas)-
mfcd00069912
bdbm50506041
(s)-2-amino-4-(2-aminophenyl)-4-oxobutanoicacid
CS-0022016
HY-104026
(alphas)-alpha,2-diamino-3-hydroxy-gamma-oxo-benzenebutanoate
(s)-alpha,2-diamino-3-hydroxy-gamma-oxo-benzenebutanoate
dl-kynureninefree base
(s)-alpha,2-diamino-3-hydroxy-gamma-oxo-benzenebutanoic acid
alpha,2-diamino-gamma-oxo-benzenebutanoate
(alphas)-alpha,2-diamino-3-hydroxy-gamma-oxo-benzenebutanoic acid
alpha,2-diamino-gamma-oxo-benzenebutanoic acid
l-2-amino-3-(2-aminobenzoyl)propionic acid l-2-amino-4-[2-aminophenyl]-4-oxobutanoic acid l-kynurenine l-kynurenine free base
BCP20697
Q415768
CS-13161
beta-anthraniloyl-l-alanine, l-2-amino-4-(2-aminophenyl)-4-oxobutanoic acid
AKOS016843487
EN300-244590
kynurenine (l)
DTXSID101031182
2-amino-4-(2-aminophenyl)-4-oxobutanoic acid
CHEBI:28683 ,
benzenebutanoic acid, .alpha.,2-diamino-.gamma.-oxo-
alanine, 3-anthraniloyl-
DIVK1C_006426
KBIO1_001370
SDCCGMLS-0066734.P001
BSPBIO_002482
SPECTRUM4_001916
SPECTRUM_001162
SPECTRUM5_000632
(+/-)-kynurenine
alanine, 3-anthraniloyl- (8ci)
dl-kynurenine
alpha-2-diamino-gamma-oxobenzenebutyric acid
.alpha.-2-diamino-.gamma.-oxobenzenebutyric acid
2-amino-4-(2-aminophenyl)-4-oxobutyric acid
benzenebutanoic acid, alpha,2-diamino-gamma-oxo-
benzenebutanoic acid, alpha,2-diamino-gamma-oxo- (9ci)
2-amino-3-(2-aminobenzoyl)propionic acid
3-anthraniloylalanine
kynurenine
343-65-7
C01718
NCGC00095648-02
NCGC00095648-01
KBIOGR_002539
KBIO2_001642
KBIO2_006778
KBIO3_001702
KBIO2_004210
KBIOSS_001642
SPECTRUM2_001380
SPBIO_001340
SPECTRUM3_000781
SPECPLUS_000330
SPECTRUM1500879
dl-kynurenine, free base
K-9002
dl-kynurenine sulfate (salt) monohydrate
K-9000
dl-kynurenine, >=95.0% (nt)
bdbm31880
AD0899CA-9379-461E-BD7D-45908947C589
3039-10-9
CCG-38856
NCGC00017339-02
NCGC00017339-03
unii-298m20b2au
(+-)-kynurenine
einecs 206-445-9
298m20b2au ,
alanine, 3-anthraniloyl-, dl-
FT-0627925
FT-0600475
FT-0600276
AKOS015894416
3-anthraniloyl-dl-alanine
CHEMBL1377927
SCHEMBL20874
kynurenine [mi]
kynurenine, dl-
kynurenine, (+/-)-
STL453545
sr-05000002450
SR-05000002450-1
alpha,2-diamino-gamma-oxobenzenebutanoic acid
Q32908783
HY-W014504
mfcd00025194
2-amino-4-(2-aminophenyl)-4-oxobutanoicacid
AS-12298
DTXSID90861884
CS-W015220
D86788
rac kynurenine

Research Excerpts

Overview

Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). It functions as a peripheral zinc-regulating hormone and is converted into a 3-hydroxykynuranine–zinc–chloride complex. Kynurenin is a tryptophan metabolite that increases with age and promotes musculoskeletal dysfunction.

ExcerptReferenceRelevance
"The kynurenine pathway (KP) is a primary route for tryptophan metabolism. "( Radiosynthesis of 1-(2-[18F]Fluoroethyl)-L-Tryptophan using a One-pot, Two-step Protocol.
Averill, LW; Falchek, SJ; Kandula, VVR; Kecskemethy, HH; Langhans, SA; Nikam, RM; Yue, X, 2021
)
1.18
"Kynurenine (Kyn) is a key inducer of an immunosuppressive tumor microenvironment (TME). "( Deep learning model enables the discovery of a novel immunotherapeutic agent regulating the kynurenine pathway.
Cheon, J; Chon, HJ; Je, S; Jung, J; Kang, B; Kim, C; Kim, JH; Kong, SJ; Lee, HJ; Lee, SJ; Lee, WS; Yang, H; Yang, HJ, 2021
)
2.28
"Kynurenine functions as a peripheral zinc-regulating hormone and is converted into a 3-hydroxykynurenine–zinc–chloride complex, precipitating within the storage granules."( Tryptophan regulates
Arnesano, F; Barbanente, A; Clark, AH; Dau, H; Garay, E; Haumann, M; Missirlis, F; Nachtegaal, M; Osorio, B; Quintanar, L; Schuth, N; Tejeda-Guzmán, C; Vela, A; Vitone, D, 2022
)
1.44
"The kynurenine pathway is a major pathway of tryptophan metabolism leading to nicotinamide adenine dinucleotide (NAD+) production."( PPARs and the Kynurenine Pathway in Melanoma-Potential Biological Interactions.
Gerkowicz, A; Krasowska, D; Walczak, K, 2023
)
1.75
"The kynurenine pathway (KP) is a major route of the essential amino acid L-tryptophan (Trp) catabolism in mammalian cells."( Maternal Inflammation with Elevated Kynurenine Metabolites Is Related to the Risk of Abnormal Brain Development and Behavioral Changes in Autism Spectrum Disorder.
Fang, K; Imamura, Y; Kasahara, Y; Konishi, Y; Momono, Y; Murakami, Y; Nishiyama, T; Sakai, D; Yoshida, C, 2023
)
1.67
"Kynurenine (Kyn) is a tryptophan metabolite that increases with age and promotes musculoskeletal dysfunction. "( Orchiectomy sensitizes cortical bone in male mice to the harmful effects of kynurenine.
Alhamad, DW; Bensreti, H; Cooley, MA; Faith, H; Fulzele, S; Grater, L; Hamrick, MW; Hill, WD; Isales, CM; Johnson, M; Kaiser, H; McGee-Lawrence, ME; Parker, E; Shaver, J; Whichard, WC; Yu, K; Zhong, R, 2023
)
2.58
"Kynurenine (Kyn) is a circulating tryptophan (Trp) catabolite generated by enzymes including IDO1 that are induced by inflammatory cytokines such as interferon-gamma. "( The kynurenine pathway in HIV, frailty and inflammaging.
Belin de Chantemèle, E; Bensreti, H; Elengickal, A; Hamrick, MW; McGee-Lawrence, ME; Sultana, S, 2023
)
2.91
"Kynurenine (KYN) is a circulating tryptophan metabolite that is known to increase with age and is a ligand of the aryl hydrocarbon receptor (Ahr)."( Kynurenine, a Tryptophan Metabolite That Increases with Age, Induces Muscle Atrophy and Lipid Peroxidation.
Fulzele, S; Hamrick, MW; Isales, CM; Johnson, M; Kaiser, H; McGee-Lawrence, ME; Mendhe, B; Pandya, C; Yu, K, 2019
)
2.68
"l-Kynurenine (KYN) is a metabolite of the Kynurenine pathway and is a known potential marker of immune suppressant disorders and cancer. "( Development of Molecularly Imprinted 2D Photonic Crystal Hydrogel Sensor for Detection of L-Kynurenine in Human Serum.
Irfan, M; Meng, ZH; Murtaza, G; Qu, F; Rizvi, AS; Xue, M; Yan, D, 2020
)
1.5
"The kynurenine pathway (KP) is a strategic metabolic system that combines regulation of neuronal excitability via glutamate receptor function and neuroinflammation via other KP metabolites. "( A randomized cross-over trial to define neurophysiological correlates of AV-101 N-methyl-D-aspartate receptor blockade in healthy veterans.
Iqbal, T; Lijffijt, M; Mathew, SJ; Murphy, N; Ramakrishnan, N; Smith, MA; Swann, AC; Vo-Le, B, 2021
)
1.18
"Kynurenine is an endogenous aryl hydrocarbon receptor (AhR) ligand."( The aryl hydrocarbon receptor facilitates the human cytomegalovirus-mediated G1/S block to cell cycle progression.
Naseri-Nosar, P; Nogalski, MT; Shenk, T, 2021
)
1.34
"Kynurenine is an intermediate in the inflammatory cascade and can be peripherally measured to proxy inflammatory activity."( Tryptophan breakdown and cognition in bipolar disorder.
Bengesser, SA; Birner, A; Dalkner, N; Fellendorf, FT; Fuchs, D; Hamm, C; Herzog-Eberhard, S; Hörmanseder, C; Kainzbauer, N; Maget, A; Mangge, H; Mansur, RB; McIntyre, RS; Moll, N; Pilz, R; Platzer, M; Queissner, R; Rauch, P; Reininghaus, EZ; Schütze, G; Schwarz, MJ; Zelzer, S, 2017
)
1.18
"The kynurenine pathway is a cascade of enzymatic steps generating biologically active compounds. "( Systemic administration of l-kynurenine sulfate induces cerebral hypoperfusion transients in adult C57Bl/6 mice.
Bari, F; Farkas, E; Gellért, L; Kis, Z; Menyhárt, Á; Puskás, T; Toldi, J; Varga, DP; Vécsei, L, 2017
)
1.3
"Kynurenine is a photo-oxidation product of tryptophan, expected to be detected when hair is exposed mainly to UVB (290-320nm) radiation range."( Tryptophan and kynurenine determination in human hair by liquid chromatography.
Baby, AR; Dario, MF; Freire, TB; Pinto, CASO; Prado, MSA; Velasco, MVR, 2017
)
1.53
"Kynurenine is a tryptophan metabolite that plays a crucial role in cancer and the immune system."( Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR).
Bradfield, CA; Chen, H; Cortopassi, M; Feltenberger, JB; Ge, Y; Jefcoate, CR; Lin, Z; Ma, ZX; Satyshur, KA; Scarlett, C; Seok, SH; Tang, W; Xing, Y, 2018
)
1.52
"The kynurenine pathway is a complex enzymatic cascade of tryptophan catabolism, generating various neuroactive metabolites."( Ischemic Stroke and Kynurenines: Medicinal Chemistry Aspects.
Fülöp, F; Hertelendy, P; Toldi, J; Vécsei, L, 2018
)
1.29
"Kynurenine (KYN) is a metabolite of tryptophan, proposed for the treatment of corneal diseases. "( Examination of Kynurenine Toxicity on Corneal and Conjunctival Epithelium: In vitro and in vivo Studies.
Czuczwar, M; Jünemann, A; Matysik-Woźniak, A; Paduch, R; Piwowarczyk, P; Rejdak, R; Turska, M; Turski, WA; Łańcut, M, 2019
)
2.31
"Kynurenine pathway (KP) is a major route of the tryptophan (TRP) catabolism. "( Early kynurenine pathway activation following cardiac arrest in rats, pigs, and humans.
Bagnati, R; Brücken, A; Brunelli, L; Derwall, M; Fries, M; Fumagalli, F; Latini, R; Li Volti, G; Masson, S; Pastorelli, R; Ristagno, G; Russo, I; Staszewsky, L; Zappalà, A, 2013
)
2.31
"Kynurenine is a potent endothelium-derived vasodilator. "( Urinary excretion of kynurenine and tryptophan, cardiovascular events, and mortality after elective coronary angiography.
Ebbing, M; Igland, J; Nilsen, RM; Nordrehaug, JE; Nygård, O; Pedersen, ER; Schartum-Hansen, H; Seifert, R; Svingen, GF; Ueland, PM, 2013
)
2.15
"Kynurenines are a wide range of catabolites which derive from tryptophan through the "Kynurenine Pathway" (KP). "( The Kynurenine Pathway in the Acute and Chronic Phases of Cerebral Ischemia.
Ballesteros, I; Cuartero, MI; de la Parra, J; García-Culebras, A; Lizasoain, I; Moro, MÁ, 2016
)
2.44
"Kynurenine (KYN) is an endothelium-derived relaxing factor that makes a large contribution to sepsis pathophysiology."( Bone Marrow Mesenchymal Stem Cells Alleviate Extracellular Kynurenine Levels, as Detected by High-Performance Liquid Chromatography.
Huang, Y; Li, D; Li, M; Pan, J; Quan, S; Tan, L; Wang, Y; Zhao, J, 2015
)
1.38
"The kynurenine pathway is a fundamental mechanism of immunosuppression and peripheral tolerance. "( Expression of the Kynurenine Pathway in Human Peripheral Blood Mononuclear Cells: Implications for Inflammatory and Neurodegenerative Disease.
Brew, BJ; Brown, DA; de Bie, J; Franco, NF; Guillemin, GJ; Jones, SP; Lim, CK; Sundaram, G; Varney, B, 2015
)
1.31
"The kynurenine pathway is a promising novel target via which to influence the immune system and to achieve neuroprotection, and further research is therefore needed with the aim of developing novel drugs for the treatment of multiple sclerosis and other autoimmune diseases."( Kynurenines and Multiple Sclerosis: The Dialogue between the Immune System and the Central Nervous System.
Majláth, Z; Pukoli, D; Rajda, C; Vécsei, L, 2015
)
2.34
"Kynurenine is a potential contributor to hypotension in animal and human sepsis. "( Kynurenine causes vasodilation and hypotension induced by activation of KCNQ-encoded voltage-dependent K(+) channels.
Akahori, T; Feng, GG; Fujiwara, Y; Hatakeyama, N; Kinoshita, H; Li, J; Nakamura, E; Sakakibara, K; Yasuda, Y, 2015
)
3.3
"Kynurenine is a circulating metabolite from the essential amino acid tryptophan. "( Impact of Plasma Kynurenine Level on Functional Capacity and Outcome in Heart Failure - Results From Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF).
Anker, SD; Doehner, W; Dschietzig, TB; Ebner, N; Konishi, M; Schefold, JC; Springer, J; von Haehling, S, 2016
)
2.22
"L-kynurenine is a tryptophan metabolite, which may render activated T-cells apoptotic and therefore might modulate an allogenous transplant reaction."( Function of the tryptophan metabolite, L-kynurenine, in human corneal endothelial cells.
Aboul-Enein, F; Höftberger, R; Lahdou, I; Scheuerle, A; Serbecic, N, 2009
)
1.18
"The kynurenine pathway (KP) is a major route of tryptophan metabolism. "( Kynurenine and its metabolites in Alzheimer's disease patients.
Bien, B; Gulaj, E; Pawlak, D; Pawlak, K, 2010
)
2.36
"Kynurenine is a small molecule derived from tryptophan when this amino acid is metabolised via the kynurenine pathway. "( Kynurenine metabolism in health and disease.
Kolodziej, LR; Paleolog, EM; Williams, RO, 2011
)
3.25
"The kynurenine pathway (KP) is a major degradative pathway of tryptophan ultimately leading to the production of NAD(+) and is also one of the major regulatory mechanisms of the immune response."( Characterization of the kynurenine pathway in NSC-34 cell line: implications for amyotrophic lateral sclerosis.
Brew, BJ; Chen, Y; Guillemin, GJ, 2011
)
1.16
"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."( Enzymatic transamination of D-kynurenine generates kynurenic acid in rat and human brain.
Amori, L; Notarangelo, FM; Pérez-de la Cruz, V; Sathyasaikumar, KV; Schwarcz, R; Wang, XD; Wu, HQ, 2012
)
1.23
"The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading to production of a number of biologically active molecules. "( Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease.
Brew, BJ; Guillemin, GJ, 2002
)
1.2
"Kynurenine (KYN) is an intermediate in the pathway of the metabolism of tryptophan to nicotinic acid. "( Role of kynurenines in the central and peripheral nervous systems.
Németh, H; Toldi, J; Vécsei, L, 2005
)
2.21
"The kynurenine pathway (KP) is a major route of L-tryptophan catabolism leading to production of several neurobiologically active molecules. "( Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis.
Brew, BJ; Guillemin, GJ; Meininger, V, 2005
)
1.21
"L-kynurenine is a central compound of this pathway since it can change to the neuroprotective agent kynurenic acid or to the neurotoxic agent quinolinic acid."( Kynurenines, Parkinson's disease and other neurodegenerative disorders: preclinical and clinical studies.
Németh, H; Toldi, J; Vécsei, L, 2006
)
2.33
"L-Kynurenine is a major metabolite of L-tryptophan in vertebrates."( L-Kynurenine, an amino acid identified as a sex pheromone in the urine of ovulated female masu salmon.
Fusetani, N; Kamio, M; Kitamura, S; Matsunaga, S; Yamada, M; Yamazaki, F; Yambe, H, 2006
)
1.61
"The kynurenine pathway is a major route of L-tryptophan catabolism producing neuroactive metabolites implicated in neurodegeneration and immune tolerance. "( Characterization of the kynurenine pathway in human neurons.
Brew, BJ; Cullen, KM; Garner, B; Guillemin, GJ; Kapoor, V; Lim, CK; Smythe, GA; Takikawa, O, 2007
)
1.2
"L-kynurenine is a metabolic precursor of kynurenic acid, which is one of the few known endogenous N-methyl-D-aspartate receptor inhibitors. "( Neuroprotection achieved in the ischaemic rat cortex with L-kynurenine sulphate.
Agoston, M; Gigler, G; Robotka, H; Rózsa, E; Sas, K; Szénási, G; Toldi, J; Vécsei, L, 2008
)
1.31
"1-Kynurenine is suggested to be an anxiogenic and convulsigenic endogenous factor."( Structure-activity relationships in kynurenine, diazepam and some putative endogenous ligands of the benzodiazepine receptors.
Lapin, IP, 1983
)
1.1
"Kynurenine is a weak emitter of fluorescence, with an emission maximum at 480 nm on excitation at 365 nm."( Fluorescence characteristics of kynurenine and N'-formylkynurenine. Their use as reporters of the environment of tryptophan 62 in hen egg-white lysozyme.
Fukunaga, Y; Izumi, T; Katsuragi, Y; Sakiyama, F, 1982
)
1.27
"Kynurenine is an upstream metabolite in the same biochemical pathway."( Differential effects of kynurenine and tryptophan treatment on quinolinate immunoreactivity in rat lymphoid and non-lymphoid organs.
Blinder, KL; Moffett, JR; Namboodiri, MA; Venkateshan, CN, 1998
)
1.33
"L-kynurenine (L-KYN) serves as a substrate for the synthesis of neurotoxic 3-OH-kynurenine (3-OH-KYN) and neuroprotective kynurenic acid (KYNA). "( Kynurenine metabolism in Alzheimer's disease.
Baran, H; Deecke, L; Jellinger, K, 1999
)
2.47
"Kynurenine is a metabolite of tryptophan, and has been reported increased in plasma during tumor growth."( Effect of kynurenine on tryptophan-albumin binding in human plasma.
Cangiano, C; Cardelli, P; Fava, A; Giglio, RM; Laviano, A; Peverini, P; Rossi Fanelli, F, 1999
)
1.43
"Kynurenine is a metabolite of tryptophan found in the human lens and is thought to play a role in protecting the retina from UV-induced damage."( A study of kynurenine fragmentation using electrospray tandem mass spectrometry.
O'Hair, RA; Sheil, MM; Truscott, RJ; Vazquez, S; Weimann, A, 2001
)
1.42
"Kynurenine is a metabolite of the tryptophan-nicotine-amide-adenine-dinucleotide pathway. "( [Kynurenine and its metabolites in nervous system diseases].
Schwab, F; Vécsei, L, 1992
)
2.64
"Kynurenine is a direct precursor of kynurenic acid, the only known endogenous antagonist of excitatory amino acid receptors in the brain. "( Kynurenine and probenecid inhibit pentylenetetrazol- and NMDLA-induced seizures and increase kynurenic acid concentrations in the brain.
Beal, MF; MacGarvey, U; Miller, J; Vécsei, L, 1992
)
3.17
"Kynurenine hydroxylase is a useful gene product for studying the events of imaginal disc differentiation."( Developmental and genetic studies on kynurenine hydroxylase from Drosophila melanogaster.
Kitos, RJ; Sullivan, DT; Sullivan, MC, 1973
)
1.25

Effects

Kynurenine pathway (KP) has a principal role in the metabolism of tryptophan. KP has a major role in seizures, inflammation as well as depression.

The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA) The pathway has been proposed as a target for modulating drug abuse.

ExcerptReferenceRelevance
"The kynurenine pathway (KP) has a principal role in the metabolism of tryptophan. "( Gene expression of indoleamine and tryptophan dioxygenases and three long non-coding RNAs in breast cancer.
Dashti, S; Ghafouri-Fard, S; Kholghi Oskooei, V; Samsami, M; Taheri, M; Taherian-Esfahani, Z, 2020
)
1.12
"Kynurenine pathway has an interwoven correlation with immune system."( The footprint of kynurenine pathway in every cancer: a new target for chemotherapy.
Ala, M, 2021
)
1.68
"Kynurenine pathway (KP) has a major role in seizures, inflammation as well as depression, considering which we evaluated the effect of LCM on kynurenine levels in murine model of neuroinflammation-mediated seizures."( Effect of lacosamide on neuroinflammation-mediated seizures comorbid with depression in C57BL/6 mice- Role of kynurenine pathway.
Agarwal, S; Nirwan, N; Vohora, D; Vyas, P, 2021
)
1.55
"The kynurenine pathway (KP) has been linked to alterations in glutamatergic and monoaminergic neurotransmission and to SZ symptomatology through the production of the metabolites quinolinic acid (QA) and kynurenic acid (KYNA)."( Kynurenine pathway in post-mortem prefrontal cortex and cerebellum in schizophrenia: relationship with monoamines and symptomatology.
Afia, AB; Artuch, R; Garcia-Bueno, B; Haro, JM; Leza, JC; MacDowell, KS; Ormazabal, A; Ramos, B; Vila, È, 2021
)
2.54
"The kynurenine pathway (KP) has been considered an important player in inflammation and immune response."( Kynurenine pathway of tryptophan metabolism in patients with familial Mediterranean fever.
Gülcemal, S; Hakbilen, S; Körez, MK; Onmaz, DE; Sivrikaya, A; Tezcan, D; Yılmaz, S, 2023
)
2.83
"The kynurenine pathway has been proposed as a target for modulating drug abuse. "( Influx of kynurenine into the brain is involved in the reduction of ethanol consumption induced by Ro 61-8048 after chronic intermittent ethanol in mice.
Colado, MI; Gil de Biedma-Elduayen, L; Giménez-Gómez, P; Gutiérrez-López, MD; Morales-Puerto, N; Núñez-de la Calle, C; O'Shea, E; Vidal, R, 2022
)
1.68
"The kynurenine pathway (KP) has a principal role in the metabolism of tryptophan. "( Gene expression of indoleamine and tryptophan dioxygenases and three long non-coding RNAs in breast cancer.
Dashti, S; Ghafouri-Fard, S; Kholghi Oskooei, V; Samsami, M; Taheri, M; Taherian-Esfahani, Z, 2020
)
1.12
"The kynurenine pathway (KP) has been proposed as indirect link between systemic immune responses and clinical symptom development in schizophrenia spectrum disorders (SSD). "( Blood-based kynurenine pathway alterations in schizophrenia spectrum disorders: A meta-analysis.
Coppens, V; De Picker, L; Kampen, JK; Morrens, M, 2020
)
1.5
"The kynurenine pathway has been proposed to play a key role between peripheral inflammation and alterations in the central nervous system."( The role of the kynurenine pathway and quinolinic acid in adolescent major depressive disorder.
Aydemir, Ö; Kandemir, H; Öztürk, M; Taneli, F; Yalın Sapmaz, Ş, 2021
)
1.45
"Kynurenine pathway has an interwoven correlation with immune system."( The footprint of kynurenine pathway in every cancer: a new target for chemotherapy.
Ala, M, 2021
)
1.68
"Kynurenine pathway (KP) has a major role in seizures, inflammation as well as depression, considering which we evaluated the effect of LCM on kynurenine levels in murine model of neuroinflammation-mediated seizures."( Effect of lacosamide on neuroinflammation-mediated seizures comorbid with depression in C57BL/6 mice- Role of kynurenine pathway.
Agarwal, S; Nirwan, N; Vohora, D; Vyas, P, 2021
)
1.55
"l-Kynurenine has antinociceptive effects in acute and inflammatory pain. "( The L-kynurenine-probenecid combination reduces neuropathic pain in rats.
Aguilera, P; Barragán-Iglesias, P; Bravo-Hernández, M; Cervantes-Durán, C; González-Esquivel, DF; Granados-Soto, V; Pérez-Severiano, F; Pineda-Farias, JB; Ríos, C, 2013
)
1.59
"The kynurenine pathway (KP) has been implicated in the development of neurodegenerative processes, and alterations in the KP have been demonstrated in both acute and chronic neurological disorders."( The potential role of kynurenines in Alzheimer's disease: pathomechanism and therapeutic possibilities by influencing the glutamate receptors.
Majláth, Z; Toldi, J; Vécsei, L, 2014
)
1.2
"The kynurenine pathway has received increasing attention as its connection to inflammation, the immune system and neurological conditions has become more apparent. "( What is the tryptophan kynurenine pathway and why is it important to neurotherapeutics?
Davis, I; Liu, A, 2015
)
1.29
"Kynurenines have been implicated in the neuroendocrine regulatory processes."( [Stress and the kynurenine pathway].
Majláth, Z; Vécsei, L, 2015
)
1.48
"The kynurenine pathway has been implicated in both the physiological processes of the central nervous system and in the pathomechanism of several neurological disorders as well."( Kynurenine System and Multiple Sclerosis, Pathomechanism and Drug Targets with An Emphasis on Laquinimod.
Annus, A; Majlath, Z; Vecsei, L, 2018
)
2.4
"Kynurenine production has been considered as a unit function of the cell as a whole rather than of the enzyme alone, and it has been concluded that even though cells in different parts of the body perform this same function (kynurenine production), the gene loci regulating this function may be different for cells in different regions of the body."( MUTANT GENES REGULATING THE INDUCIBILITY OF KYNURENINE SYNTHESIS.
RIZKI, TM, 1964
)
1.22

Actions

The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. Kynurenin promotes T Reg (regulatory) differentiation, which leads to increased production of anti-inflammatory cytokines.

ExcerptReferenceRelevance
"Kynurenine metabolites inhibit T-cell proliferation resulting in cell growth arrest."( The involvement of a chemokine receptor antagonist CTCE-9908 and kynurenine metabolites in cancer development.
Basson, C; Bipath, P; Hlophe, Y; Joubert, AM; Nkandeu, DS; Nyakudya, T; Serem, JC, 2022
)
1.68
"The kynurenine (KYN) pathway plays an important role in degrading molecules responsible for oxidative stress in the central nervous system (CNS), but can also have neurotoxic effects. "( Impaired metabolism of kynurenine and its metabolites in CSF of parkinson's disease.
Iwaoka, K; Kato, K; Maeda, T; Otsuka, C; Takahashi, K; Terayama, Y; Yamahara, K, 2020
)
1.43
"Kynurenine promotes T Reg (regulatory) differentiation, which leads to increased production of anti-inflammatory cytokines and suppression of cytotoxic activity of T cells."( The footprint of kynurenine pathway in every cancer: a new target for chemotherapy.
Ala, M, 2021
)
1.68
"The kynurenine pathway (KP) plays a critical role in generating cellular energy in the form of nicotinamide adenine dinucleotide (NAD+). "( The kynurenine pathway: a finger in every pie.
Savitz, J, 2020
)
1.67
"Kynurenine-induced increase in mRNA levels for NGF occurred as early as 1 h after the addition of the compound, peaked at 4 h and declined thereafter."( Tryptophan and its metabolite, kynurenine, stimulate expression of nerve growth factor in cultured mouse astroglial cells.
Dong-Ruyl, L; Nakano, K; Sawada, M, 1998
)
1.31

Treatment

Kynurenine inhibited glutamatergic activity in non-seizure control samples but not in MTLE-HS samples. Treatment raised forebrain KYNA levels ∼3-fold at PD2 and ∼2.5- fold at PD21.

ExcerptReferenceRelevance
"Only kynurenine-treated rats were impaired in acquiring the extra-dimensional shift (saline, 8.2; kynurenine, 21.3)."( Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine.
Alexander, KS; Bruno, JP; Schwarcz, R; Wu, HQ, 2012
)
0.83
"l-Kynurenine treatment raised forebrain KYNA levels ∼3-fold at PD2 and ∼2.5-fold at PD21."( Early developmental elevations of brain kynurenic acid impair cognitive flexibility in adults: reversal with galantamine.
Alexander, KS; Bruno, JP; Pershing, ML; Pocivavsek, A; Schwarcz, R; Wu, HQ, 2013
)
0.95
"Treatment with kynurenine inhibited glutamatergic activity in non-seizure control samples but not in MTLE-HS samples."( Altered hippocampal kynurenine pathway metabolism contributes to hyperexcitability in human mesial temporal lobe epilepsy-hippocampal sclerosis.
Banerjee Dixit, A; Banerjee, J; Chandra, PS; Dey, S; Doddamani, RS; Lalwani, S; Sharma, MC; Tripathi, M, 2021
)
1.28

Toxicity

ExcerptReferenceRelevance
" These data suggest a direct role for H2O2 and metal ions in the cytotoxic action of 3HK and indicate that cell lysis results from the intracellular accumulation of toxic levels of H2O2."( The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine.
Eastman, CL; Guilarte, TR, 1990
)
0.51
" KYNA antagonizes the toxic action of quinolinic acid (QUIN), an endogenous NMDA receptor agonist."( Systemic DL-kynurenine and probenecid pretreatment attenuates quinolinic acid-induced neurotoxicity in rats.
Altagracia, M; González-Reynoso, L; Kravzov, J; Ordaz-Moreno, J; Ríos, C; Santamaría, A; Solís-Hernández, F, 1996
)
0.67
" While peripheral loading of 30 mg/kg dose of KYN had no protective effects on L-Glu induced neurotoxicity, 300 mg/kg dose prevented the above toxic effects following intracortical L-Glu."( In vivo neuroprotective effects of peripheral kynurenine on acute neurotoxicity induced by glutamate in rat cerebral cortex.
Babu, GN; Kumar, A, 2010
)
0.62
" In this work we investigated the effect that a systemic administration of L-KYN+PROB exerted on the toxic model induced by 6-OHDA in rats."( Protective effect of L-kynurenine and probenecid on 6-hydroxydopamine-induced striatal toxicity in rats: implications of modulating kynurenate as a protective strategy.
Carrillo-Mora, P; Colín-Barenque, L; García, E; González-Herrera, IG; Pedraza-Chaverrí, J; Pérez-De La Cruz, V; Santamaría, A; Silva-Adaya, D; Villeda-Hernández, J,
)
0.44
" The toxic effects of 3-hydroxy-L-kynurenine are mediated by free radicals."( Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: novel therapeutic strategies for neurodegenerative disorders.
Fülöp, F; Klivényi, P; Szalárdy, L; Toldi, J; Vécsei, L; Zádori, D, 2012
)
0.89
"Although adverse health effects produced by lead (Pb) have long been recognized, studies regarding the immunotoxic effects of occupational exposure report conflicting results."( Assessment of immunotoxicity parameters in individuals occupationally exposed to lead.
Fuchs, D; García-Lestón, J; Laffon, B; Mayan, O; Méndez, J; Moreira, AO; Pásaro, E; Roma-Torres, J; Schroecksnadel, S; Teixeira, JP, 2012
)
0.38
"The adverse effects of D-tryptophan and the possibility of it being a surrogate index for predicting adverse effects in rats were investigated."( The urinary ratio of 3-hydroxykynurenine/3-hydroxyanthranilic acid is an index to predicting the adverse effects of D-tryptophan in rats.
Fukuwatari, T; Ohno, T; Sano, M; Shibata, K, 2014
)
0.69
" In this study, we investigated whether indoleamine 2,3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy."( Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1.
Fujigaki, H; Imamura, Y; Ishibashi, T; Kim, HC; Kubo, H; Mamiya, T; Mitani, S; Murakami, Y; Nabeshima, T; Nishikawa, M; Ohta, Y; Saito, K; Takahashi, Y; Takakura, Y; Tashiro, T; Tomita, E; Watcharanurak, K; Yamamoto, Y, 2016
)
0.43
" Ten CNS toxicities were graded according to the ACTG adverse events scale."( Tryptophan metabolism and its relationship with central nervous system toxicity in people living with HIV switching from efavirenz to dolutegravir.
Boasso, A; Fuchs, D; Higgs, C; Keegan, MR; Nelson, M; Winston, A, 2019
)
0.51
" In humans, LKYN was safe and well-tolerated at all dose levels examined."( Phase 1 study to access safety, tolerability, pharmacokinetics, and pharmacodynamics of kynurenine in healthy volunteers.
Abou-Kassem, D; Al-Karagholi, MA; Ashina, M; Bergquist, J; Hansen, JM; Hansted, AK; Jansen-Olesen, I; Ubhayasekera, K; Vécsei, L, 2021
)
0.84
" However, a broad complex ventricular tachycardia was observed in this subject, which was judged to be a Serious Adverse Event (SAE) and resulted in early termination of the study."( Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo-controlled first-in-human study in healthy volunteers.
Bergeal, M; Crause, M; Cui, Y; Dimelow, R; Fernando, D; Gorey, C; Guiney, W; Krug, AW; Muya, C; Parker, C; Robertson, N; Soleman, S; Uings, I; Vlasakakis, G; Walsh, S; Wright, W; Zhu, X, 2022
)
0.94

Pharmacokinetics

ExcerptReferenceRelevance
"In order to complete pharmacokinetic studies on the central vs."( Labeled kynurenine pharmacokinetic modeling studies in gerbils. Nonequilibrium between infused and endogenous kynurenine.
Heyes, MP; Kita, T; Markey, SP; Morrison, PF, 1999
)
0.74
" Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N'-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg."( Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy.
Chao, MW; Chao, YS; Chen, YL; Cheng, MF; Hsiao, W; Hsieh, CL; Huang, HL; Hung, MS; Kuo, CC; Liao, FY; Lin, LM; Lin, SY; Pan, SL; Peng, YH; Shih, C; Song, JS; Sun, M; Ueng, SH; Wu, JS; Wu, MH; Wu, SY; Yang, CY; Yeh, TK, 2016
)
0.43
" By in vitro and in vivo experiments, pharmacokinetic differences of two closely related analogs, S-EPA and EPA was investigated in this study."( Pharmacokinetics of S-EPA, and its inhibition on indoleamine 2,3-dioxgenase: a case of sulfur-substitution affecting distributions in blood cells.
Dong, L; Du, G; Liu, Z; Sun, H; Tian, J; Wang, W; Ye, L; Zhuang, X, 2019
)
0.51
"805 L/hr and a terminal half-life between 31."( Assessment of the safety, pharmacokinetics and pharmacodynamics of GSK3335065, an inhibitor of kynurenine monooxygenase, in a randomised placebo-controlled first-in-human study in healthy volunteers.
Bergeal, M; Crause, M; Cui, Y; Dimelow, R; Fernando, D; Gorey, C; Guiney, W; Krug, AW; Muya, C; Parker, C; Robertson, N; Soleman, S; Uings, I; Vlasakakis, G; Walsh, S; Wright, W; Zhu, X, 2022
)
0.94

Compound-Compound Interactions

Kynurenic acid does not cross the BBB, its precursor, kynurenine, if combined with probenecid, crosses it readily. The present investigation tested the hypothesis of whether kyn Laurenine protects second-order trigeminal neurons against stimulation arriving via central processes.

ExcerptReferenceRelevance
" Although kynurenic acid does not cross the BBB, its precursor, kynurenine, if combined with probenecid, crosses it readily."( Kynurenine in combination with probenecid mitigates the stimulation-induced increase of c-fos immunoreactivity of the rat caudal trigeminal nucleus in an experimental migraine model.
Chadaide, Z; Fenyo, R; Knyihár-Csillik, E; Krisztin-Péva, B; Mihály, A; Németh, H; Toldi, J; Vécsei, L, 2007
)
2.02
" The present investigation tested the hypothesis of whether kynurenine in combination with systemically administered probenecid protects second-order trigeminal neurons against stimulation arriving via central processes of trigeminal ganglion cells."( Prevention of electrical stimulation-induced increase of c-fos immunoreaction in the caudal trigeminal nucleus by kynurenine combined with probenecid.
Chadaide, Z; Fenyo, R; Knyihár-Csillik, E; Krisztin-Péva, B; Németh, H; Toldi, J; Vécsei, L, 2007
)
0.79
" Since NMDA receptors play a crucial role in trigeminal pain processing, the aim of our experiments was to compare the effects of L-kynurenine (L-KYN) combined with probenecid (PROB) or with 2-(2-N,N-dimethylaminoethylamine-1-carbonyl)-1H-quinolin-4-one hydrochloride alone, a newly synthetized KYNA derivative, on the NTG-induced nNOS expression in the rat TNC."( l-kynurenine combined with probenecid and the novel synthetic kynurenic acid derivative attenuate nitroglycerin-induced nNOS in the rat caudal trigeminal nucleus.
Bohár, Z; Fülöp, F; Párdutz, A; Tajti, J; Toldi, J; Vámos, E; Varga, H; Vécsei, L, 2009
)
1.28
" This study investigated the safety, tolerability and pharmacokinetics of navoximod alone and in combination with atezolizumab in Japanese patients with advanced solid tumours."( Phase I study of the indoleamine 2,3-dioxygenase 1 inhibitor navoximod (GDC-0919) as monotherapy and in combination with the PD-L1 inhibitor atezolizumab in Japanese patients with advanced solid tumours.
Ebata, T; Fujiwara, Y; Inatani, M; Iwasa, S; Kitano, S; Kondo, S; Koyama, T; Nakai, K; Sato, N; Shimizu, T; Shimomura, A; Tamura, K; Yamamoto, N; Yonemori, K, 2020
)
0.56
" This study explored the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor activity of LY3381916 monotherapy and in combination with a programmed death-ligand 1 (PD-L1) inhibitor (LY3300054) in patients with advanced solid tumors."( A Phase I Study of an IDO-1 Inhibitor (LY3381916) as Monotherapy and in Combination With an Anti-PD-L1 Antibody (LY3300054) in Patients With Advanced Cancer.
Bendell, J; Benhadji, KA; Doman, TN; Galvao, VR; Gandhi, L; Geeganage, S; Jalal, S; Kotecki, N; O'Neil, BH; Prenen, H; Rottey, S; Saha, A; Suriyapperuma, S; Szpurka, AM; Vuagnat, P; Wallin, J; Xia, M; Xu, X, 2021
)
0.62

Bioavailability

Tryptophan or tryptophan metabolites mediate some of the physiological or pathological aspects of the inflammatory response. Three potential therapeutic strategies could be feasible to develop drugs to live up to expectations. Prodrugs of KYNA which easily cross the blood-brain barrier combined with an inhibitor of organic acid transport for enhancement of the brain KYNA concentration.

ExcerptReferenceRelevance
"In the course of evaluating the hypothesis that tryptophan or tryptophan metabolites mediate some of the physiological or pathological aspects of the inflammatory response, we assessed the bioavailability of tryptophan and kynurenine in renal allograft recipients during periods of stable graft function, acute rejection and OKT3 therapy."( Inflammation-associated changes in the cellular availability of tryptophan and kynurenine in renal transplant recipients.
Bermes, EW; Holmes, EW; Kinzler, GJ; Russell, PM, 1994
)
0.7
" Three potential therapeutic strategies could be feasible to develop drugs to live up to expectations: (1) chemically related drugs with better bioavailability and higher affinity to the binding sites of excitatory receptors; (2) prodrugs of KYNA, which easily cross the blood-brain barrier combined with an inhibitor of organic acid transport for enhancement of the brain KYNA concentration; (3) inhibitors of enzymes of the kynurenine pathway."( The role of kynurenines in the pathomechanism of amyotrophic lateral sclerosis and multiple sclerosis: therapeutic implications.
Bencsik, K; Füvesi, J; Rajda, C; Toldi, J; Vécsei, L, 2012
)
0.92
" These findings indicate that stroke patients with PSF have a lower bioavailability of TRP for 5-HT synthesis in the brain in the acute stroke phase."( Activation of the kynurenine pathway in the acute phase of stroke and its role in fatigue and depression following stroke.
Amthor, KF; Ormstad, H; Sandvik, L; Verkerk, R, 2014
)
0.74
" Further lead optimization to improve in vitro potencies and pharmacokinetic profiles resulted in N'-(4-bromophenyl)-2-oxo-2,3-dihydro-1H-indole-5-sulfonyl hydrazide 40, which demonstrated 59% oral bioavailability and 73% of tumor growth delay without apparent body weight loss in the murine CT26 syngeneic model, after oral administration of 400 mg/kg."( Phenyl Benzenesulfonylhydrazides Exhibit Selective Indoleamine 2,3-Dioxygenase Inhibition with Potent in Vivo Pharmacodynamic Activity and Antitumor Efficacy.
Chao, MW; Chao, YS; Chen, YL; Cheng, MF; Hsiao, W; Hsieh, CL; Huang, HL; Hung, MS; Kuo, CC; Liao, FY; Lin, LM; Lin, SY; Pan, SL; Peng, YH; Shih, C; Song, JS; Sun, M; Ueng, SH; Wu, JS; Wu, MH; Wu, SY; Yang, CY; Yeh, TK, 2016
)
0.43
" quinolinic acid, an excitotoxin and N-Methyl-d-Aspartate (NMDA) receptor agonist), while in turn enhancing the bioavailability of the neuroprotective metabolites such as kynurenic acid."( Recent evidence for an expanded role of the kynurenine pathway of tryptophan metabolism in neurological diseases.
Brew, BJ; Guillemin, GJ; Jacobs, K; Lennon, MJ; Lim, CK; Lovelace, MD; Sundaram, G; Varney, B, 2017
)
0.72
" In this review, we discuss the possible influence of carbohydrates, polyphenols, lipids and proteins colonic fermentation on production, bioavailability and biological activity of metabolites linked to the gut-microbiota-brain axis."( Current evidence linking diet to gut microbiota and brain development and function.
Ceppa, F; Mancini, A; Tuohy, K, 2019
)
0.51
" This stimulation induces indoleamine 2,3-dioxygenase (IDO), an enzyme that reduces the tryptophan bioavailability to synthesize serotonin."( Chronic Mild Stress Alters Kynurenine Pathways Changing the Glutamate Neurotransmission in Frontal Cortex of Rats.
Caso, JR; García-Bueno, B; Leza, JC; Madrigal, JLM; Martín-Hernández, D; Tendilla-Beltrán, H, 2019
)
0.81
" It involves multiple pathways including interference with the bioavailability of tryptophan central to the synthesis of the neurotransmitter serotonin."( Role of Kynurenine pathway and its metabolites in mood disorders: A systematic review and meta-analysis of clinical studies.
Arnone, D; Dantzer, R; Salem, H; Saraykar, S; Selvaraj, S; Teixeira, AL, 2018
)
0.92
"Through structural modification of an oxalamide derived chemotype, a novel class of highly potent, orally bioavailable IDO1-specific inhibitors was identified."( Discovery of highly potent heme-displacing IDO1 inhibitors based on a spirofused bicyclic scaffold.
Albers, M; Anderhub, S; Czekańska, M; Hoffmann, T; Hornberger, M; Kinzel, O; Mallinger, A; Morschhaeuser, B; Pinto, S; Sonnek, C; Steeneck, C; Wang, Y, 2021
)
0.62
"Urine and serum serotonin concentrations were found to be significantly lower in AD compared with controls, suggesting the bioavailability of the neurotransmitter may be altered in the disease."( Metabolic phenotyping reveals a reduction in the bioavailability of serotonin and kynurenine pathway metabolites in both the urine and serum of individuals living with Alzheimer's disease.
Chappell, KE; D'Hondt, E; Holmes, E; Hye, A; Jiménez, B; Kłoszewska, I; Legido-Quigley, C; Lewis, MR; Lovestone, S; Mecocci, P; Snowden, SG; Soininen, H; Swann, JR; Tsolaki, M; Vellas, B; Whiley, L, 2021
)
0.85
" To exploit possibilities of TDO inhibitory treatment, development of further selective TDO inhibitor compounds with good bioavailability features and models adequately replicating PD symptoms of systemic origin should be prioritized."( Tryptophan 2,3-dioxygenase, a novel therapeutic target for Parkinson's disease.
Boros, FA; Vécsei, L, 2021
)
0.62
" Bioavailability of tryptophan is an absolute requirement for proper cell functioning and synthesis of hormones, whereas its degradation products can cause cell death."( Indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2 activity and severe course of COVID-19.
Bugiani, M; Dijkhuis, A; Duitman, JW; Geeraerts, Z; Guo, L; Lutter, R; Nossent, EJ; Roos, E; Schurink, B; van der Valk, P; van Vught, L; Vaz, FM; Vlaar, AP; Yeh, SR, 2022
)
0.72
"Boosting KYNA levels, through interference with the KP enzymes or through application of prodrugs/analogs with high bioavailability and potency, is a promising clinical approach."( Kynurenic acid in neurodegenerative disorders-unique neuroprotection or double-edged sword?
Ostapiuk, A; Urbanska, EM, 2022
)
0.72
"Chronic systemic inflammation reduces the bioavailability of circulating endothelial progenitor cells (EPCs)."( A tryptophan metabolite prevents depletion of circulating endothelial progenitor cells in systemic low-grade inflammation.
Bagaglia, F; Bianconi, V; Colangelo, C; Cosentini, E; Cucci, A; Fallarino, F; Figorilli, F; Follenzi, A; Franceschini, L; Fuchs, D; Gargaro, M; Giglioni, F; Mannarino, MR; Manni, G; Mencarelli, G; Padiglioni, E; Pieroni, B; Pirro, M; Puccetti, P; Ricciuti, D; Scalisi, G, 2023
)
0.91

Dosage Studied

Quinolinic acid appeared to be the only kynurenine metabolite which induced locomotor excitement and clonic seizures in rats. In high dosage all exhibited convulsant action in mice.

ExcerptRelevanceReference
"A spectrofluorometric assay system for tryptophan oxygenase was used to compare dosage compensation properties and ontogenic expression of suppressed, "transformed," and wild-type vermilion flies."( Dosage compensation and ontogenic expression of suppressed and transformed Vermilion flies in Drosophila.
Tobler, JE, 1975
)
0.25
" In rats there is no ratio between the dosage used and the levels of the metabolites excreted."( Effects of two different loading doses of L-tryptophan on the urinary excretion of tryptophan metabolites in rats, mice and guinea pigs. Correlation with the enzyme activities.
Allegri, G; Baccichetti, F; Biasiolo, M; Costa, C,
)
0.13
" In both groups, they measure tryptophan metabolites before and after L-tryptophan overload, the dosage being 100/mg/kg of body weight."( [Tryptophan metabolism in children with epilepsy].
Bayés García, R; del Castillo, ML; Maldonado Lozano, J; Molina Font, JA; Narbona López, E; Núñez del Carril, J; Robles Vizcaíno, C, 1984
)
0.27
"When introduced intracerebroventricularly, quinolinic acid appeared to be the only kynurenine metabolite among those tested (L- and DL-kynurenine sulfate, kynurenic and nicotinic acids, nicotinamide) which induced locomotor excitement and clonic seizures in rats; in high dosage all exhibited convulsant action in mice."( Excitatory effects of kynurenine and its metabolites, amino acids and convulsants administered into brain ventricles: differences between rats and mice.
Kiseleva, IP; Lapin, IP; Prakhie, IB, 1982
)
0.8
" The blue fluorophore was formed first and appeared then to be photochemically converted to the green one, with the rate of formation of the latter increasing with an increase in UV dosage or oxidizing conditions."( Model studies on the photochemical production of lenticular fluorophores.
Dillon, J; Ellozy, AR; Wang, RH, 1994
)
0.29
" Even though the endogenous levels of KA in rat brain are below this limit of detection, this methodology could be used to monitor the increase of KA levels in rat brain following dosing with its precursors, tryptophan and kynurenine."( Determination of kynurenic acid by capillary electrophoresis with laser-induced fluorescence detection.
Hansen, DK; Lunte, SM, 1997
)
0.48
"(1:4, mol/mol) CaPterin exerts significant (by Spearman rank order correlation) dose-response antitumor activity in nude mice with MDA-MB-231 xenographs, and sustains both inflammatory and anti-inflammatory changes in the levels of certain plasma factors."( Cytokine and IDO metabolite changes effected by calcium pterin during inhibition of MDA-MB-231 xenograph tumors in nude mice.
DiPasquale, AG; Fuchs, D; Moheno, P; Pfleiderer, W; Rheingold, AL, 2008
)
0.35
" The dose-response relation between CRP and B-6 vitamers at day 28 was nonlinear, with an increased steepness of slope at CRP >7 mg/L."( Association of plasma B-6 vitamers with systemic markers of inflammation before and after pyridoxine treatment in patients with stable angina pectoris.
Midttun, Ø; Nygård, O; Pedersen, ER; Ueland, PM; Ulvik, A, 2012
)
0.38
" In the H2O2/FeCl3/ascorbic acid variant of the deoxyribose degradation assay, the dose-response curve was U-shaped."( Quinolinic acid: neurotoxin or oxidative stress modulator?
Chobot, V; Hadacek, F; Kubicova, L, 2013
)
0.39
" Our results suggest that RT alters IDO-mediated immune status in NSCLC patients and that changes in this serum biomarker may be useful to predict outcomes and perhaps personalize RT dosage to improve survival."( IDO Immune Status after Chemoradiation May Predict Survival in Lung Cancer Patients.
Huang, L; Jin, JY; Jolly, S; Kong, FS; Li, L; Mellor, AL; Pi, W; Wang, W; Wu, H; Yan, L; Zang, Y, 2018
)
0.48
" For some parameters, U-shaped or inverted U-shaped dose-response curves are shown."( Breast cancer progression and kynurenine pathway enzymes are induced by hexachlorobenzene exposure in a Her2-positive model.
Candolfi, M; Chiappini, FA; Miret, NV; Monczor, F; Nicola Candia, AJ; Pontillo, CA; Randi, AS; Zappia, CD; Zárate, LV, 2023
)
1.2
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (3)

RoleDescription
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Saccharomyces cerevisiae metaboliteAny fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae).
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (6)

ClassDescription
kynurenineA ketone that is alanine in which one of the methyl hydrogens is substituted by a 2-aminobenzoyl group.
non-proteinogenic L-alpha-amino acidAny L-alpha-amino acid which is not a member of the group of 23 proteinogenic amino acids.
amino acid zwitterionThe zwitterionic form of an amino acid having a negatively charged carboxyl group and a positively charged amino group.
substituted aniline
aromatic ketoneA ketone in which the carbonyl group is attached to an aromatic ring.
non-proteinogenic alpha-amino acidAny alpha-amino acid which is not a member of the group of 23 proteinogenic amino acids.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (18)

PathwayProteinsCompounds
Metabolism14961108
Amino acid and derivative metabolism250260
Histidine, lysine, phenylalanine, tyrosine, proline and tryptophan catabolism4485
Tryptophan catabolism1426
Tryptophan Metabolism1855
NAD Metabolism1435
Tryptophan degradation ( Tryptophan degradation )6454
NAD biosynthesis II from tryptophan024
Selenium micronutrient network095
NAD biosynthesis II (from tryptophan)024
Biochemical pathways: part I0466
NAD+ biosynthetic pathways014
Kynurenine pathway and links to cell senescence2024
Pleural mesothelioma28
T cell modulation in pancreatic cancer459
tryptophan degradation I (via anthranilate)09
tryptophan degradation via kynurenine016
NAD biosynthesis (from tryptophan)020

Protein Targets (8)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
phosphopantetheinyl transferaseBacillus subtilisPotency70.79460.141337.9142100.0000AID1490
regulator of G-protein signaling 4Homo sapiens (human)Potency0.15000.531815.435837.6858AID504845
Chain A, Putative fructose-1,6-bisphosphate aldolaseGiardia intestinalisPotency17.74070.140911.194039.8107AID2451
Chain A, 2-oxoglutarate OxygenaseHomo sapiens (human)Potency28.18380.177814.390939.8107AID2147
phosphopantetheinyl transferaseBacillus subtilisPotency85.39730.141337.9142100.0000AID1490
Microtubule-associated protein tauHomo sapiens (human)Potency10.00000.180013.557439.8107AID1460
nuclear receptor ROR-gamma isoform 1Mus musculus (house mouse)Potency19.95060.00798.23321,122.0200AID2546; AID2551
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (31)

Processvia Protein(s)Taxonomy
blood vessel developmentAryl hydrocarbon receptorHomo sapiens (human)
regulation of adaptive immune responseAryl hydrocarbon receptorHomo sapiens (human)
negative regulation of T cell mediated immune response to tumor cellAryl hydrocarbon receptorHomo sapiens (human)
regulation of DNA-templated transcriptionAryl hydrocarbon receptorHomo sapiens (human)
regulation of transcription by RNA polymerase IIAryl hydrocarbon receptorHomo sapiens (human)
xenobiotic metabolic processAryl hydrocarbon receptorHomo sapiens (human)
apoptotic processAryl hydrocarbon receptorHomo sapiens (human)
response to xenobiotic stimulusAryl hydrocarbon receptorHomo sapiens (human)
response to toxic substanceAryl hydrocarbon receptorHomo sapiens (human)
regulation of gene expressionAryl hydrocarbon receptorHomo sapiens (human)
cAMP-mediated signalingAryl hydrocarbon receptorHomo sapiens (human)
intracellular receptor signaling pathwayAryl hydrocarbon receptorHomo sapiens (human)
regulation of B cell proliferationAryl hydrocarbon receptorHomo sapiens (human)
circadian regulation of gene expressionAryl hydrocarbon receptorHomo sapiens (human)
negative regulation of DNA-templated transcriptionAryl hydrocarbon receptorHomo sapiens (human)
positive regulation of DNA-templated transcriptionAryl hydrocarbon receptorHomo sapiens (human)
positive regulation of transcription by RNA polymerase IIAryl hydrocarbon receptorHomo sapiens (human)
negative regulation of inflammatory responseAryl hydrocarbon receptorHomo sapiens (human)
cellular response to molecule of bacterial originAryl hydrocarbon receptorHomo sapiens (human)
cellular response to cAMPAryl hydrocarbon receptorHomo sapiens (human)
cellular response to forskolinAryl hydrocarbon receptorHomo sapiens (human)
cellular response to 2,3,7,8-tetrachlorodibenzodioxineAryl hydrocarbon receptorHomo sapiens (human)
tryptophan catabolic processKynureninaseHomo sapiens (human)
NAD biosynthetic processKynureninaseHomo sapiens (human)
quinolinate biosynthetic processKynureninaseHomo sapiens (human)
response to type II interferonKynureninaseHomo sapiens (human)
'de novo' NAD biosynthetic process from tryptophanKynureninaseHomo sapiens (human)
response to vitamin B6KynureninaseHomo sapiens (human)
anthranilate metabolic processKynureninaseHomo sapiens (human)
L-kynurenine catabolic processKynureninaseHomo sapiens (human)
tryptophan catabolic process to kynurenineKynureninaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (19)

Processvia Protein(s)Taxonomy
nuclear receptor activityAryl hydrocarbon receptorHomo sapiens (human)
transcription cis-regulatory region bindingAryl hydrocarbon receptorHomo sapiens (human)
DNA-binding transcription factor activity, RNA polymerase II-specificAryl hydrocarbon receptorHomo sapiens (human)
cis-regulatory region sequence-specific DNA bindingAryl hydrocarbon receptorHomo sapiens (human)
TFIID-class transcription factor complex bindingAryl hydrocarbon receptorHomo sapiens (human)
transcription coactivator bindingAryl hydrocarbon receptorHomo sapiens (human)
DNA bindingAryl hydrocarbon receptorHomo sapiens (human)
DNA-binding transcription factor activityAryl hydrocarbon receptorHomo sapiens (human)
nuclear receptor activityAryl hydrocarbon receptorHomo sapiens (human)
protein bindingAryl hydrocarbon receptorHomo sapiens (human)
TBP-class protein bindingAryl hydrocarbon receptorHomo sapiens (human)
protein homodimerization activityAryl hydrocarbon receptorHomo sapiens (human)
protein heterodimerization activityAryl hydrocarbon receptorHomo sapiens (human)
Hsp90 protein bindingAryl hydrocarbon receptorHomo sapiens (human)
RNA polymerase II-specific DNA-binding transcription factor bindingAryl hydrocarbon receptorHomo sapiens (human)
E-box bindingAryl hydrocarbon receptorHomo sapiens (human)
sequence-specific double-stranded DNA bindingAryl hydrocarbon receptorHomo sapiens (human)
pyridoxal phosphate bindingKynureninaseHomo sapiens (human)
kynureninase activityKynureninaseHomo sapiens (human)
protein homodimerization activityKynureninaseHomo sapiens (human)
3-hydroxykynureninase activityKynureninaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (11)

Processvia Protein(s)Taxonomy
nucleusAryl hydrocarbon receptorHomo sapiens (human)
nuclear aryl hydrocarbon receptor complexAryl hydrocarbon receptorHomo sapiens (human)
nucleusAryl hydrocarbon receptorHomo sapiens (human)
nucleoplasmAryl hydrocarbon receptorHomo sapiens (human)
cytoplasmAryl hydrocarbon receptorHomo sapiens (human)
cytosolAryl hydrocarbon receptorHomo sapiens (human)
chromatinAryl hydrocarbon receptorHomo sapiens (human)
transcription regulator complexAryl hydrocarbon receptorHomo sapiens (human)
protein-containing complexAryl hydrocarbon receptorHomo sapiens (human)
cytosolic aryl hydrocarbon receptor complexAryl hydrocarbon receptorHomo sapiens (human)
aryl hydrocarbon receptor complexAryl hydrocarbon receptorHomo sapiens (human)
nucleoplasmKynureninaseHomo sapiens (human)
mitochondrionKynureninaseHomo sapiens (human)
cytosolKynureninaseHomo sapiens (human)
cytoplasmKynureninaseHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (23)

Assay IDTitleYearJournalArticle
AID412640Activity of human kynureninase N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID412643Activity of human kynureninase H102W/S332G/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID1443641Activity at Cytophaga hutchinsonii KMO assessed as NADPH consumption by UV/Vis spectrophotometer
AID412648Ratio of kcat to Km for human kynureninase H102W/S332G/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID513343Binding affinity to Bacillus subtilis 168 1A1 lysine riboswitch 179 lysc by in-line probing assay2007Nature chemical biology, Jan, Volume: 3, Issue:1
Antibacterial lysine analogs that target lysine riboswitches.
AID412641Activity of human kynureninase S332G/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID412647Ratio of kcat to Km for human kynureninase H102W/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID412646Ratio of kcat to Km for human kynureninase S332G/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID1527835Inhibition of AhR (unknown origin)2020European journal of medicinal chemistry, Jan-01, Volume: 185Targeting Aryl hydrocarbon receptor for next-generation immunotherapies: Selective modulators (SAhRMs) versus rapidly metabolized ligands (RMAhRLs).
AID513357Antibacterial activity against Bacillus subtilis 168 1A1 after 24 hrs by CLSI method2007Nature chemical biology, Jan, Volume: 3, Issue:1
Antibacterial lysine analogs that target lysine riboswitches.
AID513346Inhibition of wild-type Bacillus subtilis 168 1A1 lysine riboswitch 179 lysc assessed as reduction of beta-galactosidase activity at 5 mM after 3 hrs by lacZ reporter gene assay2007Nature chemical biology, Jan, Volume: 3, Issue:1
Antibacterial lysine analogs that target lysine riboswitches.
AID412637Activity of human wild type kynureninase2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID1443642Ratio of Kcat to Km for Cytophaga hutchinsonii KMO
AID1226028Activity of recombinant human IDO assessed as retention time treated with L-Trp by HPLC analysis2015ACS medicinal chemistry letters, Mar-12, Volume: 6, Issue:3
N (1)-Fluoroalkyltryptophan Analogues: Synthesis and in vitro Study as Potential Substrates for Indoleamine 2,3-Dioxygenase.
AID412642Activity of human kynureninase H102W/N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID412644Ratio of kcat to Km for human wild type kynureninase2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID412645Ratio of kcat to Km for human kynureninase N333T mutant2009Journal of medicinal chemistry, Jan-22, Volume: 52, Issue:2
Crystal structure of the Homo sapiens kynureninase-3-hydroxyhippuric acid inhibitor complex: insights into the molecular basis of kynureninase substrate specificity.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1159550Human Phosphogluconate dehydrogenase (6PGD) Inhibitor Screening2015Nature cell biology, Nov, Volume: 17, Issue:11
6-Phosphogluconate dehydrogenase links oxidative PPP, lipogenesis and tumour growth by inhibiting LKB1-AMPK signalling.
AID977602Inhibition of sodium fluorescein uptake in OATP1B3-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID977599Inhibition of sodium fluorescein uptake in OATP1B1-transfected CHO cells at an equimolar substrate-inhibitor concentration of 10 uM2013Molecular pharmacology, Jun, Volume: 83, Issue:6
Structure-based identification of OATP1B1/3 inhibitors.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (4,020)

TimeframeStudies, This Drug (%)All Drugs %
pre-19901031 (25.65)18.7374
1990's355 (8.83)18.2507
2000's505 (12.56)29.6817
2010's1225 (30.47)24.3611
2020's904 (22.49)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 57.59

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index57.59 (24.57)
Research Supply Index8.36 (2.92)
Research Growth Index4.91 (4.65)
Search Engine Demand Index99.88 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (57.59)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials0 (0.00%)5.53%
Trials115 (2.78%)5.53%
Reviews1 (14.29%)6.00%
Reviews509 (12.30%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies23 (0.56%)4.05%
Observational0 (0.00%)0.25%
Observational28 (0.68%)0.25%
Other6 (85.71%)84.16%
Other3,462 (83.68%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]