Kynurenine-3-monooxygenase: A review of structure, mechanism, and inhibitors

Research output: Contribution to journalReview articleResearchpeer-review

Abstract

Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway (KP), which is the major catabolic route of tryptophan. Kyn represents a branch point of the KP, being converted into the neurotoxin 3-hydroxykynurenine via KMO, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, KMO is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) diseases. Although a neurological target, administration of KMO inhibitors in the periphery has demonstrated promising pharmacological results. In light of a recent crystal structure release and reports of preclinical candidates, here we provide a concise yet comprehensive update on the current state of research into the enzymology of KMO and related drug discovery efforts, highlighting areas where further work is required.

LanguageEnglish
Pages315-324
Number of pages10
JournalDrug Discovery Today
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2016

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Kynurenine 3-Monooxygenase
Kynurenine
Mixed Function Oxygenases
Kynurenic Acid
Huntington Disease
Neurotoxins
Neuroprotective Agents
Drug Discovery
Tryptophan
Parkinson Disease
Pharmacology

Cite this

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abstract = "Kynurenine monooxygenase (KMO) is an enzyme of the kynurenine (Kyn) pathway (KP), which is the major catabolic route of tryptophan. Kyn represents a branch point of the KP, being converted into the neurotoxin 3-hydroxykynurenine via KMO, neuroprotectant kynurenic acid, and anthranilic acid. As a result of this branch point, KMO is an attractive drug target for several neurodegenerative and/or neuroinflammatory diseases, especially Huntington's (HD), Alzheimer's (AD), and Parkinson's (PD) diseases. Although a neurological target, administration of KMO inhibitors in the periphery has demonstrated promising pharmacological results. In light of a recent crystal structure release and reports of preclinical candidates, here we provide a concise yet comprehensive update on the current state of research into the enzymology of KMO and related drug discovery efforts, highlighting areas where further work is required.",
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Kynurenine-3-monooxygenase : A review of structure, mechanism, and inhibitors. / Smith, Jason R.; Jamie, Joanne F.; Guillemin, Gilles J.

In: Drug Discovery Today, Vol. 21, No. 2, 02.2016, p. 315-324.

Research output: Contribution to journalReview articleResearchpeer-review

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