University of Leicester
Browse
KMO review for flavin symposium master revision clean.pdf (815.94 kB)

Advantages of brain penetrating inhibitors of kynurenine-3-monooxygenase for treatment of neurodegenerative diseases

Download (815.94 kB)
journal contribution
posted on 2021-01-07, 10:52 authored by Shaowei Zhang, Mary EW Collier, Derren J Heyes, Flaviano Giorgini, Nigel S Scrutton
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.

History

Citation

Archives of Biochemistry and Biophysics Volume 697, 15 January 2021, 108702

Author affiliation

Department of Genetics and Genome Biology

Version

  • AM (Accepted Manuscript)

Published in

Archives of biochemistry and biophysics

Volume

697

Pagination

108702

Publisher

Elsevier BV

issn

0003-9861

eissn

1096-0384

Acceptance date

2020-11-24

Copyright date

2020

Available date

2021-12-01

Spatial coverage

United States

Language

eng

Usage metrics

    University of Leicester Publications

    Categories

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC