Major developments in the design of inhibitors along the kynurenine pathway

Kelly R. Jacobs, Gloria Castellano-Gonzalez, Gilles J. Guillemin, David B. Lovejoy

Research output: Contribution to journalReview article

20 Citations (Scopus)

Abstract

Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity. The field seems poised to yield one or more inhibitors that should find clinical utility.

Original languageEnglish
Pages (from-to)2471-2495
Number of pages25
JournalCurrent medicinal chemistry
Volume24
Issue number23
DOIs
Publication statusPublished - 2017

Keywords

  • 3-dioxygenase
  • cancer
  • enzyme inhibitors
  • indoleamine 2
  • kynurenine 3- monooxygenase
  • Kynurenine pathway
  • neurodegeneration

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