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Major Developments in the Design of Inhibitors along the Kynurenine Pathway

[ Vol. 24 , Issue. 23 ]

Author(s):

Kelly R. Jacobs, Gloria Castellano-Gonzalez , Gilles J. Guillemin * and David B. Lovejoy *   Pages 2471 - 2495 ( 25 )

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.

Keywords:

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

Affiliation:

Neuroinflammation Group, Department of Biomedical Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Neuroinflammation Group, Department of Biomedical Research, Faculty of Medicine and Health Sciences, Macquarie University, Sydney, Department of Biomedical Research, Faculty of Medicine and Health Science, Macquarie University, 2 Technology Place, Sydney, Department of Biomedical Research, Faculty of Medicine and Health Science, Macquarie University, 2 Technology Place, Sydney



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