Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases.
Brain penetrance
Inhibitor
Kynurenine-3-monooxygenase
Neurodegenerative disease
Prodrug
Journal
Archives of biochemistry and biophysics
ISSN: 1096-0384
Titre abrégé: Arch Biochem Biophys
Pays: United States
ID NLM: 0372430
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
07
10
2020
revised:
18
11
2020
accepted:
24
11
2020
pubmed:
5
12
2020
medline:
2
2
2021
entrez:
4
12
2020
Statut:
ppublish
Résumé
Kynurenine-3-monooxygenase (KMO) is an important therapeutic target for several brain disorders that has been extensively studied in recent years. Potent inhibitors towards KMO have been developed and tested within different disease models, showing great therapeutic potential, especially in models of neurodegenerative disease. The inhibition of KMO reduces the production of downstream toxic kynurenine pathway metabolites and shifts the flux to the formation of the neuroprotectant kynurenic acid. However, the efficacy of KMO inhibitors in neurodegenerative disease has been limited by their poor brain permeability. Combined with virtual screening and prodrug strategies, a novel brain penetrating KMO inhibitor has been developed which dramatically decreases neurotoxic metabolites. This review highlights the importance of KMO as a drug target in neurological disease and the benefits of brain permeable inhibitors in modulating kynurenine pathway metabolites in the central nervous system.
Identifiants
pubmed: 33275878
pii: S0003-9861(20)30711-6
doi: 10.1016/j.abb.2020.108702
pmc: PMC8111166
mid: NIHMS1698811
pii:
doi:
Substances chimiques
Enzyme Inhibitors
0
Kynurenine 3-Monooxygenase
EC 1.14.13.9
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108702Subventions
Organisme : NIMH NIH HHS
ID : P50 MH103222
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Références
J Med Chem. 1994 Mar 4;37(5):647-55
pubmed: 8126705
J Neurochem. 2010 Jun;113(6):1416-25
pubmed: 20236387
Adv Exp Med Biol. 2003;527:167-76
pubmed: 15206729
Asian J Pharm Sci. 2020 Mar;15(2):131-144
pubmed: 32373195
Neurosci Lett. 2020 Jan 1;714:134576
pubmed: 31654722
J Clin Invest. 1996 Jun 1;97(11):2517-24
pubmed: 8647944
Molecules. 2008 May 01;13(5):1035-65
pubmed: 18560328
Adv Exp Med Biol. 1996;398:171-5
pubmed: 8906262
J Neurol Sci. 1992 Mar;108(1):80-7
pubmed: 1385624
J Parkinsons Dis. 2017;7(4):577-587
pubmed: 29103054
Nat Rev Drug Discov. 2010 May;9(5):387-98
pubmed: 20431570
Nat Med. 2016 Feb;22(2):202-9
pubmed: 26752518
Nature. 2013 Apr 18;496(7445):382-5
pubmed: 23575632
Cell. 1994 May 20;77(4):491-502
pubmed: 7910522
Gene. 2007 Jul 1;396(1):203-13
pubmed: 17499941
Proc Natl Acad Sci U S A. 2016 May 10;113(19):5435-40
pubmed: 27114543
Neuropathol Appl Neurobiol. 2005 Aug;31(4):395-404
pubmed: 16008823
Pharmacol Rep. 2013;65(1):1-14
pubmed: 23563019
J Med Chem. 1997 Dec 19;40(26):4378-85
pubmed: 9435907
Exp Neurol. 2016 Aug;282:99-118
pubmed: 27163548
Cell. 2011 Jun 10;145(6):863-74
pubmed: 21640374
J Biochem. 1998 Feb;123(2):253-62
pubmed: 9538200
J Cell Biol. 1969 Mar;40(3):648-77
pubmed: 5765759
Science. 1983 Jan 21;219(4582):316-8
pubmed: 6849138
Commun Biol. 2019 Jul 24;2:271
pubmed: 31372510
Leukemia. 2020 Feb;34(2):567-577
pubmed: 31462737
Drug Discov Today. 2016 Feb;21(2):315-24
pubmed: 26589832
Nat Commun. 2017 Jun 12;8:15827
pubmed: 28604669
Lancet Neurol. 2019 Dec;18(12):1091-1102
pubmed: 31701892
Prog Neurobiol. 2017 Aug;155:76-95
pubmed: 27072742
J Mol Biol. 2018 Oct 12;430(20):3847-3862
pubmed: 30098337
Nat Rev Drug Discov. 2002 Aug;1(8):609-20
pubmed: 12402501
J Biochem. 2010 Dec;148(6):639-50
pubmed: 20802227
Neuropharmacology. 2013 Mar;66:133-42
pubmed: 22491023
J Neurosci Res. 2020 Jan;98(1):155-167
pubmed: 31257634
J Nutr. 2010 Jul;140(7):1220-6
pubmed: 20463145
Neurobiol Dis. 2006 Jul;23(1):190-7
pubmed: 16697652
Redox Rep. 2010;15(4):161-8
pubmed: 20663292
Nat Genet. 2005 May;37(5):526-31
pubmed: 15806102
J Neural Transm (Vienna). 2000;107(3):343-53
pubmed: 10821443
J Neuroinflammation. 2020 Jun 6;17(1):176
pubmed: 32505212
Proc Natl Acad Sci U S A. 1996 Oct 29;93(22):12553-8
pubmed: 8901620
Microvasc Res. 1985 Jul;30(1):99-115
pubmed: 4021842
Lancet. 2015 Aug 29;386(9996):896-912
pubmed: 25904081
Lancet Neurol. 2020 Feb;19(2):170-178
pubmed: 31521533
PLoS One. 2009 Jul 22;4(7):e6344
pubmed: 19623258
Nat Rev Neurosci. 2012 Jul;13(7):465-77
pubmed: 22678511
Lancet Neurol. 2011 Jan;10(1):83-98
pubmed: 21163446
Acta Neuropathol. 2006 Aug;112(2):127-37
pubmed: 16788821
Neurosci Lett. 1988 Jul 19;90(1-2):208-12
pubmed: 3412643
Biochem Biophys Res Commun. 1967 Feb 8;26(3):309-14
pubmed: 4291901
NeuroRx. 2005 Jan;2(1):3-14
pubmed: 15717053
Neurology. 1992 Sep;42(9):1702-6
pubmed: 1513457
Cell Chem Biol. 2018 Apr 19;25(4):426-438.e4
pubmed: 29429898
J Neurochem. 2009 Apr;109(2):316-25
pubmed: 19226371
Neuropharmacology. 2017 Jan;112(Pt B):346-364
pubmed: 27265569
J Mol Med (Berl). 2013 Jun;91(6):705-13
pubmed: 23636512
Biochemistry. 2008 Nov 25;47(47):12420-33
pubmed: 18954092
FEBS Lett. 1997 Jun 30;410(2-3):407-12
pubmed: 9237672
Eur J Pharmacol. 1996 Nov 21;315(3):263-7
pubmed: 8982663
J Immunol. 2019 Aug 15;203(4):899-910
pubmed: 31285277
Br J Pharmacol. 2013 Jul;169(6):1211-27
pubmed: 23647169
Biol Pharm Bull. 2017;40(11):1990-1995
pubmed: 29093349
Neuropharmacology. 2017 Jan;112(Pt B):264-274
pubmed: 26767951
Neuroscience. 1994 Jul;61(2):237-43
pubmed: 7969905
Neurosci Lett. 1992 Sep 14;144(1-2):199-201
pubmed: 1436703
Lancet. 2016 Jul 30;388(10043):505-17
pubmed: 26921134
J Med Chem. 2015 Feb 12;58(3):1159-83
pubmed: 25590515
Drug Metab Dispos. 2012 Dec;40(12):2297-306
pubmed: 22942319
Brain Res. 2012 Aug 15;1468:1-10
pubmed: 22683359
Curr Biol. 2011 Jun 7;21(11):961-6
pubmed: 21636279
J Biol Chem. 2013 Dec 20;288(51):36554-66
pubmed: 24189070
Chem Biol Interact. 2020 Jan 5;315:108884
pubmed: 31678113
Nat Rev Dis Primers. 2015 Apr 23;1:15005
pubmed: 27188817
Nat Rev Drug Discov. 2013 Jan;12(1):64-82
pubmed: 23237916
Adv Exp Med Biol. 2003;527:621-8
pubmed: 15206781
Oxid Med Cell Longev. 2013;2013:104024
pubmed: 24089628
Mol Pharmacol. 2012 May;81(5):643-56
pubmed: 22311707
Neurobiol Dis. 2004 Dec;17(3):455-61
pubmed: 15571981