The Kynurenine Pathway and Kynurenine 3-Monooxygenase Inhibitors

Molecules

Osman F. Güner¹  Emma Carine Iradukunda²  Robert S. Phillips²  J. Phillip Bowen³  Tamera D. Hughes³ 

[1] Department of Chemistry and Physics, Santa Rosa Junior College, Santa Rosa, CA 95401, USA;Department of Chemistry, University of Georgia, Athens, GA 30602, USA;Department of Pharmaceutical Sciences, College of Pharmacy, Mercer University, 3001 Mercer University Drive, Atlanta, GA 30341, USA;

关键词: neurodegenerative diseases;    Alzheimer’s disease (AD);    kynurenine 3-monooxygenase (KMO);    pharmacophore modeling;    KMO inhibitors;    kynurenine pathway (KP);   

DOI  :  10.3390/molecules27010273

来源: DOAJ

【 摘 要 】

Under normal physiological conditions, the kynurenine pathway (KP) plays a critical role in generating cellular energy and catabolizing tryptophan. Under inflammatory conditions, however, there is an upregulation of the KP enzymes, particularly kynurenine 3-monooxygenase (KMO). KMO has garnered much attention due to its production of toxic metabolites that have been implicated in many diseases and disorders. With many of these illnesses having an inadequate or modest treatment, there exists a need to develop KMO inhibitors that reduce the production of these toxic metabolites. Though prior efforts to find an appropriate KMO inhibitor were unpromising, the development of a KMO crystal structure has provided the opportunity for a rational structure-based design in the development of inhibitors. Therefore, the purpose of this review is to describe the kynurenine pathway, the kynurenine 3-monooxygenase enzyme, and KMO inhibitors and their potential candidacy for clinical use.

【 授权许可】

Unknown