2. Academic Validation
  3. Kynurenine-3-monooxygenase: a review of structure, mechanism, and inhibitors

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

  • Drug Discov Today. 2016 Feb;21(2):315-24. doi: 10.1016/j.drudis.2015.11.001.
Jason R Smith 1,  Joanne F Jamie 2,  Gilles J Guillemin 3
Affiliations

Affiliations

  • 1 Department of Chemistry and Biomolecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia.
  • 2 Department of Chemistry and Biomolecular Sciences, Faculty of Science and Engineering, Macquarie University, Sydney, NSW 2109, Australia. Electronic address: joanne.jamie@mq.edu.au.
  • 3 Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, NSW 2109, Australia.
PMID: 26589832 DOI: 10.1016/j.drudis.2015.11.001
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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