Journal
NATURE REVIEWS DRUG DISCOVERY
Volume 18, Issue 5, Pages 379-401Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41573-019-0016-5
Keywords
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Funding
- German Cancer Aid [70110392]
- German Research Foundation [DFG PL-315/5-1]
- Italian Association of Cancer Research [19903]
- Telethon [GGP17094]
- German Federal Ministry of Education and Research (BMBF) e:Med initiative (GlioPATH) [01ZX1402]
- European Research Council (ERC)
- alumni chapter of Gooische Groningers by Ubbo Emmius Fonds
- European Union [754688]
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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 indoleamine2,3-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.
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