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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Major Developments in the Design of Inhibitors along the Kynurenine Pathway

Author(s): Kelly R. Jacobs, Gloria Castellano-Gonzalez , Gilles J. Guillemin * and David B. Lovejoy *

Volume 24 , Issue 23 , 2017

Page: [2471 - 2495] Pages: 25

DOI: 10.2174/0929867324666170502123114

open access plus

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.


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