The DOI matches its Crossref record; 292 of the 292 references it cites were found in a registry or an index.
Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond
Open accessAbstract
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.
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UCSF Chimera—A visualization system for exploratory research and analysis
Pettersen, E. F., Goddard, T. D., Huang, C. C., Couch, G. S., Greenblatt, D. M., Meng, E. C., & Ferrin, T. E. (2004) · Journal of Computational Chemistry · doi:10.1002/jcc.20084 · Cited by 46,047
Tissue-based map of the human proteome
Uhlén, M., Fagerberg, L., Hallström, B. M., Lindskog, C., Oksvold, P., Mardinoglu, A., Sivertsson, Å., Kampf, C., Sjöstedt, E., Asplund, A., et al. (2015) · Science · doi:10.1126/science.1260419 · Cited by 15,286
Zelante, T., Iannitti, R. G., Cunha, C., De Luca, A., Giovannini, G., Pieraccini, G., Zecchi, R., D’Angelo, C., Massi-Benedetti, C., Fallarino, F., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.08.003 · Cited by 2,614
Self-citationPrevention of Allogeneic Fetal Rejection by Tryptophan Catabolism
Munn, D. H., Zhou, M., Attwood, J. T., Bondarev, I. E., Conway, S. J., Marshall, B., Brown, C. C., & Mellor, A. L. (1998) · Science · doi:10.1126/science.281.5380.1191 · Cited by 2,589
Ido expression by dendritic cells: tolerance and tryptophan catabolism
Mellor, A. L., & Munn, D. H. (2004) · Nature Reviews Immunology · doi:10.1038/nri1457 · Cited by 2,341
Uyttenhove, C., Pilotte, L., Théate, I., Stroobant, V., Colau, D., Parmentier, N., Boon, T., & Van den Eynde, B. J. (2003) · Nature Medicine · doi:10.1038/nm934 · Cited by 2,305
An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor
Opitz, C. A., Litzenburger, U. M., Sahm, F., Ott, M., Tritschler, I., Trump, S., Schumacher, T., Jestaedt, L., Schrenk, D., Weller, M., et al. (2011) · Nature · doi:10.1038/nature10491 · Cited by 1,898
Self-citationRomani, L. (2011) · Nature Reviews Immunology · doi:10.1038/nri2939 · Cited by 1,793
An Interaction between Kynurenine and the Aryl Hydrocarbon Receptor Can Generate Regulatory T Cells
Mezrich, J. D., Fechner, J. H., Zhang, X., Johnson, B. P., Burlingham, W. J., & Bradfield, C. A. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.0903670 · Cited by 1,674
Inhibition of T Cell Proliferation by Macrophage Tryptophan Catabolism
Munn, D. H., Shafizadeh, E., Attwood, J. T., Bondarev, I. E., Pashine, A., & Mellor, A. L. (1999) · The Journal of Experimental Medicine · doi:10.1084/jem.189.9.1363 · Cited by 1,640
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Metadata
- Authors
- Platten, M., Nollen, E. A. A., Röhrig, U. F., Fallarino, F., & Opitz, C. A.
- Affiliations
- German Cancer Research Center (DE)
- University Medical Center Groningen (NL)
- SIB Swiss Institute of Bioinformatics (CH)
- University of Perugia (IT)
- Corresponding author
- Platten, Michael
- Venue
- Nature Reviews Drug Discovery
- Published
- 2019-02-13
- Volume
- 18
- Issue
- 5
- Pages
- 379-401
- ISSN
- 1474-1776 (ISSN-L)
- 1474-1784
- OpenAlex
- W2912181843
- Cited by
- 1,586
- References
- 292
- Citations by year
- 2026: 245 · 2025: 278 · 2024: 284 · 2023: 241 · 2022: 220 · 2021: 176 · 2020: 119 · 2019: 23
- FWCI
- 8.66
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- Locations
- Nature Reviews Drug Discovery (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, other-oa)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Keywords
- tryptophan metabolism, kynurenine pathway, IDO1 inhibitors, indoleamine 2,3-dioxygenase, IDO2, tryptophan 2,3-dioxygenase, kynurenine monooxygenase, cancer immunotherapy, neurodegeneration, autoimmune disease, infectious diseases, central nervous system disorders, drug development
- MeSH terms
- Animals, Antineoplastic Agents, Clinical Trials as Topic, Humans, Neoplasms, Tryptophan, Neurodegenerative Diseases, Metabolic Networks and Pathways
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