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

Jason R. Smith, Joanne F. Jamie*, Gilles J. Guillemin

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)315-324
Number of pages10
JournalDrug Discovery Today
Volume21
Issue number2
DOIs
Publication statusPublished - Feb 2016

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