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Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic targetsDolšak, Ana, farmacevtka, 1993- ; Gobec, Stanislav, 1970- ; Sova, Matej, 1979-Conversion of tryptophan to N-formylkynurenine is the first and rate-limiting step of the tryptophan metabolic pathway (i.e., the kynurenine pathway). This conversion is catalyzed by three enzyme ... isoforms: indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan-2,3-dioxygenase (TDO). As this pathway generates numerous metabolites that are involved in various pathological conditions, IDOs and TDO represent important targets for therapeutic intervention. This pathway has especially drawn attention due to its importance in tumor resistance. Over the last decade, a large number of IDO and TDO inhibitors have been developed, many of which have entered clinical trials. Here, detailed structural comparisons of these three enzymes (with emphasis on their active sites), their involvement in cellular signaling, and their role(s) in pathological conditions are discussed. Furthermore, the most important recent inhibitors described in papers and patents and involved in clinical trials are reviewed, with a focus on both selective and multiple inhibitors. A short overview of the biochemical and cellular assays used for inhibitory potency evaluation is also presented. This review summarizes recent advances on IDO and TDO as potential drug targets, and provides the key features and perspectives for further research and development of potent kynurenine pathway inhibitors.Source: Pharmacology & therapeutics [Elektronski vir]. - ISSN 1879-016X (Vol. 221, 2021, str. 1-23)Type of material - e-article ; adult, seriousPublish date - 2021Language - englishCOBISS.SI-ID - 38739715
Author
Dolšak, Ana, farmacevtka, 1993- |
Gobec, Stanislav, 1970- |
Sova, Matej, 1979-
Topics
Imunski sistem |
Rak (medicina) |
indoleamine 2,3-dioxygenase |
tryptophan-2,3-dioxygenase |
kynurenine |
pathwayInhibitors |
immune system |
cancer |
multiple activities |
indolamin2,3-dioksigenaza |
triptofan2,3-dioksigenaza |
kinureninska pot |
zaviralci |
multiplo delovanje
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Dolšak, Ana, farmacevtka, 1993- | 50400 |
Gobec, Stanislav, 1970- | 15284 |
Sova, Matej, 1979- | 25490 |
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