PMID- 25478733
OWN - NLM
STAT- MEDLINE
DCOM- 20160129
LR  - 20211108
IS  - 1878-5832 (Electronic)
IS  - 1359-6446 (Linking)
VI  - 20
IP  - 5
DP  - 2015 May
TI  - Targeting key dioxygenases in tryptophan-kynurenine metabolism for 
      immunomodulation and cancer chemotherapy.
PG  - 609-17
LID - S1359-6446(14)00444-9 [pii]
LID - 10.1016/j.drudis.2014.11.007 [doi]
AB  - Tryptophan to kynurenine metabolism is controlled by three distinct dioxygenase 
      enzymes: tryptophan 2,3-dioxygenase (TDO), indoleamine 2,3-dioxygenase 1 (IDO1), 
      and indoleamine 2,3-dioxygenase 2 (IDO2). Collectively, the activity of these 
      enzymes contributes to tumour immune tolerance and immune dysregulation in a 
      variety of disease pathologies, including cancer. Whereas IDO1 inhibitor drug 
      design has been the focus of study for more than two decades (with novel 
      compounds currently in Phase II clinical trials), only recently have the roles of 
      TDO and IDO2 been elucidated in immunosuppression. Consequently, little 
      comparative work on inhibitor cross-reactivity and selectivity has been 
      performed. Here, we provide an overview of the current and future drug discovery 
      landscape for targeting TDO, IDO1, and IDO2 (individually and collectively) for 
      pharmacological intervention.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Austin, Christopher J D
AU  - Austin CJ
AD  - School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.
FAU - Rendina, Louis M
AU  - Rendina LM
AD  - School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia. 
      Electronic address: lou.rendina@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141203
PL  - England
TA  - Drug Discov Today
JT  - Drug discovery today
JID - 9604391
RN  - 0 (Antineoplastic Agents)
RN  - 0 (IDO1 protein, human)
RN  - 0 (IDO2 protein, human)
RN  - 0 (Immunologic Factors)
RN  - 0 (Indoleamine-Pyrrole 2,3,-Dioxygenase)
RN  - 343-65-7 (Kynurenine)
RN  - 8DUH1N11BX (Tryptophan)
RN  - EC 1.13.11.- (Dioxygenases)
RN  - EC 1.13.11.11 (Tryptophan Oxygenase)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/chemistry/*therapeutic use
MH  - Catalytic Domain
MH  - Dioxygenases/*antagonists & inhibitors/chemistry/metabolism
MH  - *Drug Discovery
MH  - Humans
MH  - Immunologic Factors/chemistry/*therapeutic use
MH  - Indoleamine-Pyrrole 2,3,-Dioxygenase/antagonists & inhibitors/metabolism
MH  - Kynurenine/*metabolism
MH  - Models, Molecular
MH  - Molecular Targeted Therapy
MH  - Protein Conformation
MH  - Structure-Activity Relationship
MH  - Tryptophan/*metabolism
MH  - Tryptophan Oxygenase/antagonists & inhibitors/metabolism
EDAT- 2014/12/06 06:00
MHDA- 2016/01/30 06:00
CRDT- 2014/12/06 06:00
PHST- 2014/09/08 00:00 [received]
PHST- 2014/10/23 00:00 [revised]
PHST- 2014/11/13 00:00 [accepted]
PHST- 2014/12/06 06:00 [entrez]
PHST- 2014/12/06 06:00 [pubmed]
PHST- 2016/01/30 06:00 [medline]
AID - S1359-6446(14)00444-9 [pii]
AID - 10.1016/j.drudis.2014.11.007 [doi]
PST - ppublish
SO  - Drug Discov Today. 2015 May;20(5):609-17. doi: 10.1016/j.drudis.2014.11.007. Epub 
      2014 Dec 3.