PMID- 33212094
OWN - NLM
STAT- MEDLINE
DCOM- 20220113
LR  - 20220113
IS  - 1879-016X (Electronic)
IS  - 0163-7258 (Linking)
VI  - 221
DP  - 2021 May
TI  - Indoleamine and tryptophan 2,3-dioxygenases as important future therapeutic 
      targets.
PG  - 107746
LID - S0163-7258(20)30277-1 [pii]
LID - 10.1016/j.pharmthera.2020.107746 [doi]
AB  - 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 inhibitors of the kynurenine pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Dolsak, Ana
AU  - Dolsak A
AD  - University of Ljubljana, Faculty of Pharmacy, Askerceva 7, SI-1000 Ljubljana, 
      Slovenia.
FAU - Gobec, Stanislav
AU  - Gobec S
AD  - University of Ljubljana, Faculty of Pharmacy, Askerceva 7, SI-1000 Ljubljana, 
      Slovenia.
FAU - Sova, Matej
AU  - Sova M
AD  - University of Ljubljana, Faculty of Pharmacy, Askerceva 7, SI-1000 Ljubljana, 
      Slovenia. Electronic address: matej.sova@ffa.uni-lj.si.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20201116
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - EC 1.13.11.11 (Tryptophan Oxygenase)
SB  - IM
MH  - Clinical Trials as Topic
MH  - Forecasting
MH  - Humans
MH  - *Indoleamine-Pyrrole 2,3,-Dioxygenase/drug effects
MH  - *Neoplasms/drug therapy
MH  - *Tryptophan Oxygenase/drug effects
OTO - NOTNLM
OT  - Cancer
OT  - Immune system
OT  - Indoleamine 2,3-dioxygenase
OT  - Inhibitors
OT  - Kynurenine pathway
OT  - Multiple activities
OT  - Tryptophan 2,3-dioxygenase
COIS- Declaration of Competing Interest The authors declare that they have no conflicts 
      of interests.
EDAT- 2020/11/20 06:00
MHDA- 2022/01/14 06:00
CRDT- 2020/11/19 20:08
PHST- 2020/08/27 00:00 [received]
PHST- 2020/11/06 00:00 [revised]
PHST- 2020/11/10 00:00 [accepted]
PHST- 2020/11/20 06:00 [pubmed]
PHST- 2022/01/14 06:00 [medline]
PHST- 2020/11/19 20:08 [entrez]
AID - S0163-7258(20)30277-1 [pii]
AID - 10.1016/j.pharmthera.2020.107746 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2021 May;221:107746. doi: 10.1016/j.pharmthera.2020.107746. Epub 
      2020 Nov 16.