Papers of special note have been highlighted as either of interest (•) or of considerable interest (••) to readers
1. Zadori D, Klivenyi P, Plangar I, et al. Endogenous neuroprotection in chronic neurodegenerative disorders: with particular regard to the kynurenines. J Cell Mol Med 2
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2011;15:701-17
• Interesting review on the treatment options in neurodegenerative disorders via natural endogenous targets.
2. Wolf H. The effect of hormones and vitamin B6 on urinary excretion of metabolites of the kynurenine pathway. Scand J Clin Lab Invest Suppl 1974;136:1-186
3. Beadle GW, Mitchell HK, Nyc JF. Kynurenine as an intermediate in the formation of nicotinic acid from tryptophane by Neurospora. Proc Natl Acad Sci U S A 1947;33:155-8 4. Vecsei L, Szalardy L, Fulop F, Toldi J. Kynurenines in the CNS: recent advances and new questions. Nat Rev Drug Discov 2013;12:64-82
•• Comprehensive review describing the role of alterations in the KYNkynurenine pathway of TRPtryptophan metabolism in certain neurological conditions.
5. Perkins MN, Stone TW. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 1982;247:184-7
6. Birch PJ, Grossman CJ, Hayes AG. Kynurenate and FG9041 have both competitive and non-competitive antagonist actions at excitatory amino acid receptors. Eur J Pharmacol 1988;151:313-5
7. Kessler M, Terramani T, Lynch G, Baudry M. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem 1989;52:1319-28
8. Rozsa E, Robotka H, Vecsei L, Toldi J. The Janus-face kynurenic acid. J Neural Transm 2008;115:1087-91
9. Hilmas C, Pereira EF, Alkondon M, et al. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression:
physiopathological implications. J Neurosci 2001;21:7463-73 2
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10. Marchi M, Risso F, Viola C, et al. Direct evidence that release-stimulating alpha7*
nicotinic cholinergic receptors are localized on human and rat brain glutamatergic axon terminals. J Neurochem 2002;80:1071-8
11. Stone TW. Kynurenic acid blocks nicotinic synaptic transmission to hippocampal interneurons in young rats. Eur J Neurosci 2007;25:2656-65
12. Arnaiz-Cot JJ, Gonzalez JC, Sobrado M, et al. Allosteric modulation of alpha 7 nicotinic receptors selectively depolarizes hippocampal interneurons, enhancing spontaneous GABAergic transmission. Eur J Neurosci 2008;27:1097-110
13. Mok MH, Fricker AC, Weil A, Kew JN. Electrophysiological characterisation of the actions of kynurenic acid at ligand-gated ion channels. Neuropharmacology 2009;57:242-9 14. Dobelis P, Staley KJ, Cooper DC. Lack of modulation of nicotinic acetylcholine alpha-7 receptor currents by kynurenic acid in adult hippocampal interneurons. PLoS One 2012;7:e41108
15. Wang J, Simonavicius N, Wu X, et al. Kynurenic acid as a ligand for orphan G protein-coupled receptor GPR35. J Biol Chem 2006;281:22021-8
16. Lugo-Huitron R, Blanco-Ayala T, Ugalde-Muniz P, et al. On the antioxidant properties of kynurenic acid: free radical scavenging activity and inhibition of oxidative stress. Neurotoxicol Teratol 2011;33:538-47
17. Eastman CL, Guilarte TR. The role of hydrogen peroxide in the in vitro cytotoxicity of 3-hydroxykynurenine. Neurochem Res 1990;15:1101-7
18. Dykens JA, Sullivan SG, Stern A. Oxidative reactivity of the tryptophan metabolites 3-hydroxyanthranilate, cinnabarinate, quinolinate and picolinate. Biochem Pharmacol 1987;36:211-7
19. Jhamandas K, Boegman RJ, Beninger RJ, Bialik M. Quinolinate-induced cortical cholinergic damage: modulation by tryptophan metabolites. Brain Res 1990;529:185-91 2
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20. de Carvalho LP, Bochet P, Rossier J. The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid discriminate between NMDAR2 receptor subunits.
Neurochem Int 1996;28:445-52
21. Liu Y, Wong TP, Aarts M, et al. NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo. J Neurosci 2007;27:2846-57 22. Connick JH, Stone TW. Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo. Br J Pharmacol 1988;93:868-76
23. Rios C, Santamaria A. Quinolinic acid is a potent lipid peroxidant in rat brain homogenates. Neurochem Res 1991;16:1139-43
24. Zadori D, Klivenyi P, Szalardy L, et al. Mitochondrial disturbances, excitotoxicity, neuroinflammation and kynurenines: novel therapeutic strategies for neurodegenerative disorders. J Neurol Sci 2012;322:187-91
25. Schwarcz R, Guidetti P, Sathyasaikumar KV, Muchowski PJ. Of mice, rats and men:
Revisiting the quinolinic acid hypothesis of Huntington's disease. Prog Neurobiol 2010;90:230-45
• An interesting review about the role of neurotoxic KYNkynurenine pathway metabolites in Huntington's disease.
26. Stone TW, Mackay GM, Forrest CM, et al. Tryptophan metabolites and brain disorders. Clin Chem Lab Med 2003;41:852-9
• An interesting review describing how the absolute or relative concentrations of neuroactive kynurenines are implicated in certain neurological conditions, such as aquired immune deficiency syndromeAIDS-dementia complex or HDHuntington's disease.
27. Schwarcz R, Rassoulpour A, Wu HQ, et al. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry 2001;50:521-30
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28. Chess AC, Simoni MK, Alling TE, Bucci DJ. Elevations of endogenous kynurenic acid produce spatial working memory deficits. Schizophr Bull 2007;33:797-804
29. Zadori D, Veres G, Szalardy L, et al. Glutamatergic dysfunctioning in Alzheimer's disease and related therapeutic targets. J Alzheimers Dis 2014;42 Suppl 3:S177-87 30. Baran H, Jellinger K, Deecke L. Kynurenine metabolism in Alzheimer's disease. J Neural Transm (Vienna) 1999;106:165-81
31. Potter MC, Elmer GI, Bergeron R, et al. Reduction of endogenous kynurenic acid formation enhances extracellular glutamate, hippocampal plasticity, and cognitive behavior.
Neuropsychopharmacology 2010;35:1734-42
32. Braidy N, Guillemin GJ, Grant R. Effects of kynurenine pathway inhibition on NAD metabolism and cell viability in human primary astrocytes and neurons. Int J Tryptophan Res 2011;4:29-37
33. De Laurentis W, Khim L, Anderson JL, et al. The second enzyme in pyrrolnitrin biosynthetic pathway is related to the heme-dependent dioxygenase superfamily.
Biochemistry 2007;46:12393-404
34. Sugimoto H, Oda S, Otsuki T, et al. Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase.
Proc Natl Acad Sci U S A 2006;103:2611-6
• This paper reports the three dimensional structure of IDO.
35. Forouhar F, Anderson JL, Mowat CG, et al. Molecular insights into substrate recognition and catalysis by tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A 2007;104:473-8
36. Zhang Y, Kang SA, Mukherjee T, et al. Crystal structure and mechanism of tryptophan 2,3-dioxygenase, a heme enzyme involved in tryptophan catabolism and in quinolinate biosynthesis. Biochemistry 2007;46:145-55
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• This paper reports the three dimensional structure of TDO.
37. Ball HJ, Sanchez-Perez A, Weiser S, et al. Characterization of an indoleamine 2,3-dioxygenase-like protein found in humans and mice. Gene 2007;396:203-13
38. Metz R, Duhadaway JB, Kamasani U, et al. Novel tryptophan catabolic enzyme IDO2 is the preferred biochemical target of the antitumor indoleamine 2,3-dioxygenase inhibitory compound D-1-methyl-tryptophan. Cancer Res 2007;67:7082-7
39. Lob S, Konigsrainer A, Schafer R, et al. Levo- but not dextro-1-methyl tryptophan abrogates the IDO activity of human dendritic cells. Blood 2008;111:2152-4
40. Lob S, Konigsrainer A, Zieker D, et al. IDO1 and IDO2 are expressed in human tumors: levo- but not dextro-1-methyl tryptophan inhibits tryptophan catabolism. Cancer Immunol Immunother 2009;58:153-7
41. Mandi Y, Vecsei L. The kynurenine system and immunoregulation. J Neural Transm (Vienna) 2012;119:197-209
42. Grozdics E, Berta L, Bajnok A, et al. B7 costimulation and intracellular indoleamine-2,3-dioxygenase (IDO) expression in peripheral blood of healthy pregnant and non-pregnant women. BMC Pregnancy Childbirth 2014;14:306
43. Kegel ME, Bhat M, Skogh E, et al. Imbalanced kynurenine pathway in schizophrenia.
Int J Tryptophan Res 2014;7:15-22
44. Sathyasaikumar KV, Stachowski EK, Wonodi I, et al. Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull 2011;37:1147-56
• This paper describes the importance of elevated prefrontal KYNAkynurenic acid level in the pathogenesis of cognitive dysfunctions in schizophrenia.
45. Vacchelli E, Aranda F, Eggermont A, et al. Trial watch: IDO inhibitors in cancer therapy. Oncoimmunology 2014;3:e957994
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46. Opitz CA, Litzenburger UM, Opitz U, et al. The indoleamine-2,3-dioxygenase (IDO) inhibitor 1-methyl-D-tryptophan upregulates IDO1 in human cancer cells. PLoS One
2011;6:e19823
47. Hou DY, Muller AJ, Sharma MD, et al. Inhibition of indoleamine 2,3-dioxygenase in dendritic cells by stereoisomers of 1-methyl-tryptophan correlates with antitumor responses.
Cancer Res 2007;67:792-801
48. Liu X, Shin N, Koblish HK, et al. Selective inhibition of IDO1 effectively regulates mediators of antitumor immunity. Blood 2010;115:3520-30
49. Mautino MR, Jaipuri FA, Waldo J, et al. NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy [abstract]. In:
Proceedings of the 104th Annual Meeting of the American Association for Cancer Research;
2013 Apr 6-10; Washington, DC Philadelphia (PA). Cancer Res 2013;73:Abstract nr 491 50. Li M, Bolduc AR, Hoda MN, et al. The indoleamine 2,3-dioxygenase pathway controls complement-dependent enhancement of chemo-radiation therapy against murine glioblastoma. J Immunother Cancer 2014;2:21
51. Salter M, Hazelwood R, Pogson CI, et al. The effects of a novel and selective inhibitor of tryptophan 2,3-dioxygenase on tryptophan and serotonin metabolism in the rat. Biochem Pharmacol 1995;49:1435-42
52. Dolusic E, Larrieu P, Moineaux L, et al. Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators. J Med Chem 2011;54:5320-34
53. Pilotte L, Larrieu P, Stroobant V, et al. Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci U S A 2012;109:2497-502 54. Yu D, Tao BB, Yang YY, et al. The IDO inhibitor coptisine ameliorates cognitive impairment in a mouse model of Alzheimer's disease. J Alzheimers Dis 2015;43:291-302 2
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55. Campesan S, Green EW, Breda C, et al. The kynurenine pathway modulates
neurodegeneration in a Drosophila model of Huntington's disease. Curr Biol 2011;21:961-6 56. Mazarei G, Budac DP, Lu G, et al. The absence of indoleamine 2,3-dioxygenase expression protects against NMDA receptor-mediated excitotoxicity in mouse brain. Exp Neurol 2013;249:144-8
57. O'Connor JC, Lawson MA, Andre C, et al. Induction of IDO by bacille Calmette-Guerin is responsible for development of murine depressive-like behavior. J Immunol 2009;182:3202-12
58. O'Connor JC, Lawson MA, Andre C, et al. Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice. Mol Psychiatry 2009;14:511-22
59. Jackman KA, Brait VH, Wang Y, et al. Vascular expression, activity and function of indoleamine 2,3-dioxygenase-1 following cerebral ischaemia-reperfusion in mice. Naunyn Schmiedebergs Arch Pharmacol 2011;383:471-81
60. Han Q, Cai T, Tagle DA, Li J. Structure, expression, and function of kynurenine aminotransferases in human and rodent brains. Cell Mol Life Sci 2010;67:353-68
61. Okuno E, Nakamura M, Schwarcz R. Two kynurenine aminotransferases in human brain. Brain Res 1991;542:307-12
62. Yu P, Li Z, Zhang L, et al. Characterization of kynurenine aminotransferase III, a novel member of a phylogenetically conserved KAT family. Gene 2006;365:111-8 63. Guidetti P, Amori L, Sapko MT, et al. Mitochondrial aspartate aminotransferase: a third kynurenate-producing enzyme in the mammalian brain. J Neurochem 2007;102:103-11 64. Guillemin GJ, Kerr SJ, Smythe GA, et al. Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J Neurochem 2001;78:842-53
•• This paper describes the kynurenine pathway in astrocytes with a special attention to 2
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KYNAkynurenic acid production.
65. Guidetti P, Hoffman GE, Melendez-Ferro M, et al. Astrocytic localization of kynurenine aminotransferase II in the rat brain visualized by immunocytochemistry. Glia 2007;55:78-92
66. Roberts RC, Du F, McCarthy KE, et al. Immunocytochemical localization of kynurenine aminotransferase in the rat striatum: a light and electron microscopic study. J Comp Neurol 1992;326:82-90
67. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain:
when physiology meets pathology. Nat Rev Neurosci 2012;13:465-77
• This interesting review delineates the role of neuroactive kynurenines in brain functioning and dysfunctioning.
68. Rossi F, Garavaglia S, Montalbano V, et al. Crystal structure of human kynurenine aminotransferase II, a drug target for the treatment of schizophrenia. J Biol Chem
2008;283:3559-66
• This paper reports the three dimensional structure of KAT-II.
69. Guidetti P, Okuno E, Schwarcz R. Characterization of rat brain kynurenine aminotransferases I and II. J Neurosci Res 1997;50:457-65
70. Battaglia G, Rassoulpour A, Wu HQ, et al. Some metabotropic glutamate receptor ligands reduce kynurenate synthesis in rats by intracellular inhibition of kynurenine aminotransferase II. J Neurochem 2000;75:2051-60
71. Luchowska E, Luchowski P, Paczek R, et al. Dual effect of DL-homocysteine and S-adenosylhomocysteine on brain synthesis of the glutamate receptor antagonist, kynurenic acid. J Neurosci Res 2005;79:375-82
72. Kocki T, Luchowski P, Luchowska E, et al. L-cysteine sulphinate, endogenous sulphur-containing amino acid, inhibits rat brain kynurenic acid production via selective 2
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interference with kynurenine aminotransferase II. Neurosci Lett 2003;346:97-100
73. Pellicciari R, Rizzo RC, Costantino G, et al. Modulators of the kynurenine pathway of tryptophan metabolism: synthesis and preliminary biological evaluation of
(S)-4-(ethylsulfonyl)benzoylalanine, a potent and selective kynurenine aminotransferase II (KAT II) inhibitor. ChemMedChem 2006;1:528-31
74. Passera E, Campanini B, Rossi F, et al. Human kynurenine aminotransferase II--reactivity with substrates and inhibitors. FEBS J 2011;278:1882-900
75. Pocivavsek A, Wu HQ, Potter MC, et al. Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology 2011;36:2357-67 76. Amori L, Guidetti P, Pellicciari R, et al. On the relationship between the two branches of the kynurenine pathway in the rat brain in vivo. J Neurochem 2009;109:316-25
77. Pellicciari R, Venturoni F, Bellocchi D, et al. Sequence variants in kynurenine aminotransferase II (KAT II) orthologs determine different potencies of the inhibitor S-ESBA. ChemMedChem 2008;3:1199-202
78. Casazza V, Rossi F, Rizzi M. Biochemical and structural investigations on kynurenine aminotransferase II: an example of conformation-driven species-specific inhibition? Curr Top Med Chem 2011;11:148-57
79. Wu HQ, Okuyama M, Kajii Y, et al. Targeting kynurenine aminotransferase II in psychiatric diseases: promising effects of an orally active enzyme inhibitor. Schizophr Bull 2014;40 Suppl 2:S152-8
80. Dounay AB, Anderson M, Bechle BM, et al. Discovery of brain-penetrant, irreversible kynurenine aminotransferase II inhibitors for schizophrenia. ACS Med Chem Lett
2012;3:187-92
81. Kozak R, Campbell BM, Strick CA, et al. Reduction of brain kynurenic acid improves cognitive function. J Neurosci 2014;34:10592-602
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82. Battie C, Verity MA. Presence of kynurenine hydroxylase in developing rat brain. J Neurochem 1981;36:1308-10
83. Smith JR, Jamie JF, Guillemin GJ. Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors. Drug Discov Today 2016;21:315-24
•• A comprehensive review on KMOkynurenine 3-monooxygenase inhibitors.
84. Espey MG, Chernyshev ON, Reinhard JF, Jr., et al. Activated human microglia produce the excitotoxin quinolinic acid. Neuroreport 1997;8:431-4
•• This paper describes the production of neurotoxic KYNkynurenine pathway metabolites in microglia.
85. Erickson JB, Flanagan EM, Russo S, Reinhard JF, Jr. A radiometric assay for kynurenine 3-hydroxylase based on the release of 3H2O during hydroxylation of L-[3,5-3H]kynurenine. Anal Biochem 1992;205:257-62
86. Guillemin GJ, Smith DG, Smythe GA, et al. Expression of the kynurenine pathway enzymes in human microglia and macrophages. Adv Exp Med Biol 2003;527:105-12
•• This paper describes the production of neurotoxic KYNkynurenine pathway metabolites in microglia.
87. Heyes MP, Chen CY, Major EO, Saito K. Different kynurenine pathway enzymes limit quinolinic acid formation by various human cell types. Biochem J 1997;326 ( Pt 2):351-6
88. Fukui S, Schwarcz R, Rapoport SI, et al. Blood-brain barrier transport of kynurenines:
implications for brain synthesis and metabolism. J Neurochem 1991;56:2007-17
• This paper describes the mechanism of the transport of kynurenines via the blood-brain barrier.
89. Crozier-Reabe KR, Phillips RS, Moran GR. Kynurenine 3-monooxygenase from Pseudomonas fluorescens: substrate-like inhibitors both stimulate flavin reduction and 2
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stabilize the flavin-peroxo intermediate yet result in the production of hydrogen peroxide.
Biochemistry 2008;47:12420-33
90. Amaral M, Levy C, Heyes DJ, et al. Structural basis of kynurenine 3-monooxygenase inhibition. Nature 2013;496:382-5
• This paper reports the three dimensional structure of KMO and the mechanism of its inhibition.
91. Carpenedo R, Chiarugi A, Russi P, et al. Inhibitors of kynurenine hydroxylase and kynureninase increase cerebral formation of kynurenate and have sedative and anticonvulsant activities. Neuroscience 1994;61:237-43
92. Harris CA, Miranda AF, Tanguay JJ, et al. Modulation of striatal quinolinate neurotoxicity by elevation of endogenous brain kynurenic acid. Br J Pharmacol 1998;124:391-9
93. Miranda AF, Boegman RJ, Beninger RJ, Jhamandas K. Protection against quinolinic acid-mediated excitotoxicity in nigrostriatal dopaminergic neurons by endogenous kynurenic acid. Neuroscience 1997;78:967-75
94. Connick JH, Heywood GC, Sills GJ, et al. Nicotinylalanine increases cerebral kynurenic acid content and has anticonvulsant activity. Gen Pharmacol 1992;23:235-9 95. Russi P, Alesiani M, Lombardi G, et al. Nicotinylalanine increases the formation of kynurenic acid in the brain and antagonizes convulsions. J Neurochem 1992;59:2076-80 96. Pellicciari R, Natalini B, Costantino G, et al. Modulation of the kynurenine pathway in search for new neuroprotective agents. Synthesis and preliminary evaluation of
(m-nitrobenzoyl)alanine, a potent inhibitor of kynurenine-3-hydroxylase. J Med Chem 1994;37:647-55
97. Moroni F, Cozzi A, Peruginelli F, et al. Neuroprotective effects of kynurenine-3-hydroxylase inhibitors in models of brain ischemia. Adv Exp Med Biol 1999;467:199-206 2
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98. Moroni F, Carpenedo R, Cozzi A, et al. Studies on the neuroprotective action of kynurenine mono-oxygenase inhibitors in post-ischemic brain damage. Adv Exp Med Biol 2003;527:127-36
99. Cozzi A, Carpenedo R, Moroni F. Kynurenine hydroxylase inhibitors reduce ischemic brain damage: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfonamide (Ro 61-8048) in models of focal or global brain ischemia. J Cereb Blood Flow Metab 1999;19:771-7
100. Behan WM, Stone TW. Role of kynurenines in the neurotoxic actions of kainic acid.
Br J Pharmacol 2000;129:1764-70
101. Chiarugi A, Moroni F. Quinolinic acid formation in immune-activated mice: studies with (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(-3-nitrophenyl)thiazol-2yl]-benzenesul fonamide (Ro 61-8048), two potent and selective inhibitors of kynurenine hydroxylase. Neuropharmacology 1999;38:1225-33
102. Speciale C, Wu HQ, Cini M, et al. (R,S)-3,4-dichlorobenzoylalanine (FCE 28833A) causes a large and persistent increase in brain kynurenic acid levels in rats. Eur J Pharmacol 1996;315:263-7
103. Speciale C, Cini M, Wu HQ, et al. Kynurenic acid-enhancing and anti-ischemic effects of the potent kynurenine 3-hydroxylase inhibitor FCE 28833 in rodents. Adv Exp Med Biol 1996;398:221-7
104. Natalini B, Mattoli L, Pellicciari R, et al. Synthesis and activity of enantiopure (S) (m-nitrobenzoyl) alanine, potent kynurenine-3-hydroxylase inhibitor. Bioorg Med Chem Lett 1995;5:1451-1454
105. Giordani A, Pevarello P, Cini M, et al. 4-Phenyl-4-oxo-butanoic acid derivatives inhibitors of kynurenine 3-hydroxylase. Bioorg Med Chem Lett 1998;8:2907-2912
106. Pellicciari R, Amori L, Costantino G, et al. Modulation of the kynurine pathway of 2
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tryptophan metabolism in search for neuroprotective agents. Focus on kynurenine-3-hydroxylase. Adv Exp Med Biol 2003;527:621-8
107. Sapko MT, Guidetti P, Yu P, et al. Endogenous kynurenate controls the vulnerability of striatal neurons to quinolinate: Implications for Huntington's disease. Exp Neurol
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108. The J. David Gladstone Institutes, a testamentary trust established under the will of J.
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109. Rover S, Cesura AM, Huguenin P, et al. Synthesis and biochemical evaluation of N-(4-phenylthiazol-2-yl)benzenesulfonamides as high-affinity inhibitors of kynurenine 3-hydroxylase. J Med Chem 1997;40:4378-85
110. Gregoire L, Rassoulpour A, Guidetti P, et al. Prolonged kynurenine 3-hydroxylase inhibition reduces development of levodopa-induced dyskinesias in parkinsonian monkeys.
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111. Ouattara B, Belkhir S, Morissette M, et al. Implication of NMDA receptors in the antidyskinetic activity of cabergoline, CI-1041, and Ro 61-8048 in MPTP monkeys with levodopa-induced dyskinesias. J Mol Neurosci 2009;38:128-42
112. Richter A, Hamann M. The kynurenine 3-hydroxylase inhibitor Ro 61-8048 improves dystonia in a genetic model of paroxysmal dyskinesia. Eur J Pharmacol 2003;478:47-52 113. Hamann M, Sander SE, Richter A. Effects of the kynurenine 3-hydroxylase inhibitor Ro 61-8048 after intrastriatal injections on the severity of dystonia in the dt sz mutant. Eur J Pharmacol 2008;586:156-9
114. Giorgini F, Guidetti P, Nguyen Q, et al. A genomic screen in yeast implicates kynurenine 3-monooxygenase as a therapeutic target for Huntington disease. Nat Genet 2
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2005;37:526-31
115. Clark CJ, Mackay GM, Smythe GA, et al. Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. Infect Immun 2005;73:5249-51 116. Rodgers J, Stone TW, Barrett MP, et al. Kynurenine pathway inhibition reduces central nervous system inflammation in a model of human African trypanosomiasis. Brain 2009;132:1259-67
117. Zwilling D, Huang SY, Sathyasaikumar KV, et al. Kynurenine 3-monooxygenase inhibition in blood ameliorates neurodegeneration. Cell 2011;145:863-74
118. Beconi MG, Yates D, Lyons K, et al. Metabolism and pharmacokinetics of JM6 in mice: JM6 is not a prodrug for Ro-61-8048. Drug Metab Dispos 2012;40:2297-306 119. Toledo-Sherman LM, Prime ME, Mrzljak L, et al. Development of a series of aryl pyrimidine kynurenine monooxygenase inhibitors as potential therapeutic agents for the treatment of Huntington's disease. J Med Chem 2015;58:1159-83
•• A comprehensive review on aryl pyrimidines as KMOkynurenine 3-monooxygenase inhibitors.
120. Guidetti P, Eastman CL, Schwarcz R. Metabolism of [5-3H]kynurenine in the rat brain in vivo: evidence for the existence of a functional kynurenine pathway. J Neurochem
1995;65:2621-32
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