Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond

Abstract:

L-Tryptophan (Trp) metabolism through the kynurenine pathway (KP) is involved in the regulation of immunity, neuronal function and intestinal homeostasis. Imbalances in Trp metabolism in disorders ranging from cancer to neurodegenerative disease have stimulated interest in therapeutically targeting the KP, particularly the main rate-limiting enzymes indoleamine-2,3-dioxygenase 1 (IDO1), IDO2 and tryptophan-2,3-dioxygenase (TDO) as well as kynurenine monooxygenase (KMO). However, although small-molecule IDO1 inhibitors showed promise in early-stage cancer immunotherapy clinical trials, a phase III trial was negative. This Review summarizes the physiological and pathophysiological roles of Trp metabolism, highlighting the vast opportunities and challenges for drug development in multiple diseases.

SEEK ID: https://fairdomhub.org/publications/424

DOI: 10.1038/s41573-019-0016-5

Projects: MESI-STRAT

Journal: Nat Rev Drug Discov

Citation: Nat Rev Drug Discov 18(5) : 379

Date Published: 1st May 2019

Authors: Michael Platten, Ellen A. A. Nollen, Ute F. Röhrig, Francesca Fallarino, Christiane Opitz

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Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A. (2019). Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nature Reviews Drug Discovery, 18(5), 379–401. http://doi.org/10.1038/s41573-019-0016-5
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Created: 1st Oct 2019 at 11:58

Last updated: 1st Oct 2019 at 12:05

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