indoleamine 2,3-dioxygenase 1 | 1.13.11.- Dioxygenases | IUPHAR Guide to IMMUNOPHARMACOLOGY

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indoleamine 2,3-dioxygenase 1

Target id: 2829

Nomenclature: indoleamine 2,3-dioxygenase 1

Abbreviated Name: IDO1

Family: 1.13.11.- Dioxygenases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: ON :     indoleamine 2,3-dioxygenase 1 has curated data in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 403 8p12-p11 IDO1 indoleamine 2,3-dioxygenase 1 2,11
Mouse - 407 8 A2 Ido1 indoleamine 2,3-dioxygenase 1
Rat - 407 16q12.5 Ido1 indoleamine 2,3-dioxygenase 1
Gene and Protein Information Comments
Two isoforms of mouse Ido1 have been identified. We list the longer of the two, isoform 1 in the table above. The shorter isoform has only 316 amino acids.
Previous and Unofficial Names
INDO | indoleamine-pyrrole 2,3 dioxygenase | IDO-1 | IDO | indoleamine 2
Database Links
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
RefSeq Nucleotide
RefSeq Protein
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the indoleamine 2,3-dioxygenagse 1 (IDO1) complexed with Amg-1.
PDB Id:  4PK5
Ligand:  amg-1
Resolution:  2.79Å
Species:  Human
References:  13
Enzyme Reaction
EC Number:

Download all structure-activity data for this target as a CSV file

Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
NLG919 Hs Inhibition 8.1 pKi 7
pKi 8.1 (Ki 7x10-9 M) [7]
compound 5i [PMID: 24099220] Hs Inhibition 7.3 pKi 15
pKi 7.3 (Ki 5.4x10-8 M) [15]
tryptanthrin Hs Inhibition 5.3 pKi 15
pKi 5.3 (Ki 4.81x10-6 M) [15]
necrostatin-1 Hs Inhibition 4.9 pKi 10
pKi 4.9 (Ki 1.16x10-5 M) [10]
Description: Using a purified recombinant human IDO enzyme for in vitro>/i> assays.
1-methyl-L-tryptophan Hs Inhibition 4.4 pKi 15
pKi 4.4 (Ki 4.23x10-5 M) [15]
beta-carboline Hs Inhibition 0.9 pKi 3
pKi 0.9 (Ki 1.2x10-1 M) [3]
epacadostat Hs Inhibition 7.2 pIC50 16
pIC50 7.2 (IC50 6.7x10-8 M) [16]
PF-06840003 Hs Inhibition 6.8 pIC50 1
pIC50 6.8 (IC50 1.5x10-7 M) [1]
Description: Measuring inhibition of IDO1-induced kynurenine production in vitro.
LW106 Hs Inhibition 5.8 pIC50 4
pIC50 5.8 (IC50 1.57x10-6 M) [4]
Description: Measuring enzyme activity in IFNγ-stimulated HeLa cells.
amg-1 Hs Inhibition 5.5 pIC50 8
pIC50 5.5 (IC50 3x10-6 M) [8]
Physiological Functions
Indoleamine 2,3-dioxygenase 1 catalyzes the degradation of L-tryptophan via the reaction L-tryptophan + O2 <=> N-formyl-L-kynurenine. L-tryptophan has an immunosuppressive effect.
Species:  Human
Tissue:  Macrophages
References:  9
IDO expression at the maternal–fetal interface depletes L-tryptophan, an effect which inhibits activation of maternal T-cells in resopnse to fetal alloantigens, thereby preventing rejection of the fetus.
Species:  Mouse
Tissue:  Decidua, placenta
References:  9
IDO expression by tumour cells, depletes L-tryptophan in the tumour microenvironment blocks T-cell proliferation thereby allowing tumour cells to evade the immune response.
Species:  Human
Tissue:  Melanoma cells, pancreatic cancer cells, non-small cell lung cancer cells, laryngeal carcinoma cells, pharyngeal squamous-cell carcinoma cells.
References:  14
General Comments
IDO1 is a rate-limiting enzyme of tryptophan catabolism along the kynurenine pathway. IDO1 catabolises both the L- and D- enantiomers of tryptophan, but shows preference for L-tryptophan. Additional IDO1 substrates include indoleamines such as serotonin, melatonin, and tryptamine [12].
IDO1 emerged as an important new therapeutic target for the treatment of cancer, neurological disorders, and other diseases that are characterized by pathological tryptophan metabolism. Despite encouraging anti-tumour activity in preclinical models and early stage clinical trials, and especially in combination with immune checkpoint inhibitors, the potential of IDO1 inhibitors may not be translated to later stage clinical efficacy. No clinical trial results have yet been published, but insiders commenting online suggest that IDO1 inhibitors may not deliver on their promise (see IDO Inhibitors Hit a Wall on Derek Lowe's In The Pipeline blog, April 9, 2018)


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1. Crosignani S, Cauwenberghs S, Driessens G, Deroose F. (2015) Pyrrolidine-2,5-dione derivatives, pharmaceutical compositions and methods for use as ido1 inhibitors. Patent number: WO2015173764. Assignee: Iteos Therapeutics. Priority date: 15/05/2014. Publication date: 19/11/2015.

2. Dai W, Gupta SL. (1990) Molecular cloning, sequencing and expression of human interferon-gamma-inducible indoleamine 2,3-dioxygenase cDNA. Biochem. Biophys. Res. Commun., 168 (1): 1-8. [PMID:2109605]

3. Dolušić E, Larrieu P, Blanc S, Sapunaric F, Norberg B, Moineaux L, Colette D, Stroobant V, Pilotte L, Colau D et al.. (2011) Indol-2-yl ethanones as novel indoleamine 2,3-dioxygenase (IDO) inhibitors. Bioorg. Med. Chem., 19 (4): 1550-61. [PMID:21269836]

4. Fu R, Zhang YW, Li HM, Lv WC, Zhao L, Guo QL, Lu T, Weiss SJ, Li ZY, Wu ZQ. (2018) LW106, a novel indoleamine 2,3-dioxygenase 1 inhibitor, suppresses tumour progression by limiting stroma-immune crosstalk and cancer stem cell enrichment in tumour micro-environment. Br. J. Pharmacol., 175 (14): 3034-3049. [PMID:29722898]

5. Holmgaard RB, Zamarin D, Munn DH, Wolchok JD, Allison JP. (2013) Indoleamine 2,3-dioxygenase is a critical resistance mechanism in antitumor T cell immunotherapy targeting CTLA-4. J. Exp. Med., 210 (7): 1389-402. [PMID:23752227]

6. Lee SM, Park HY, Suh YS, Yoon EH, Kim J, Jang WH, Lee WS, Park SG, Choi IW, Choi I et al.. (2017) Inhibition of acute lethal pulmonary inflammation by the IDO-AhR pathway. Proc. Natl. Acad. Sci. U.S.A., 114 (29): E5881-E5890. [PMID:28673995]

7. Mautino MR, Jaipuri FA, Waldo J, Kumar S, Adams J, Van Allen C, Marcinowicz-Flick A, Munn D, Vahanian N, Link CJ. Abstract 491: NLG919, a novel indoleamine-2,3-dioxygenase (IDO)-pathway inhibitor drug candidate for cancer therapy. Accessed on 09/02/2016. Modified on 09/02/2016., DOI: 10.1158/1538-7445

8. Meininger D, Zalameda L, Liu Y, Stepan LP, Borges L, McCarter JD, Sutherland CL. (2011) Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors. Biochim. Biophys. Acta, 1814 (12): 1947-54. [PMID:21835273]

9. Mellor AL, Munn DH. (1999) Tryptophan catabolism and T-cell tolerance: immunosuppression by starvation?. Immunol. Today, 20 (10): 469-73. [PMID:10500295]

10. Muller AJ, DuHadaway JB, Donover PS, Sutanto-Ward E, Prendergast GC. (2005) Inhibition of indoleamine 2,3-dioxygenase, an immunoregulatory target of the cancer suppression gene Bin1, potentiates cancer chemotherapy. Nat. Med., 11 (3): 312-9. [PMID:15711557]

11. Najfeld V, Menninger J, Muhleman D, Comings DE, Gupta SL. (1993) Localization of indoleamine 2,3-dioxygenase gene (INDO) to chromosome 8p12-->p11 by fluorescent in situ hybridization. Cytogenet. Cell Genet., 64 (3-4): 231-2. [PMID:8404046]

12. Shimizu T, Nomiyama S, Hirata F, Hayaishi O. (1978) Indoleamine 2,3-dioxygenase. Purification and some properties. J. Biol. Chem., 253 (13): 4700-6. [PMID:26687]

13. Tojo S, Kohno T, Tanaka T, Kamioka S, Ota Y, Ishii T, Kamimoto K, Asano S, Isobe Y. (2014) Crystal Structures and Structure-Activity Relationships of Imidazothiazole Derivatives as IDO1 Inhibitors. ACS Med Chem Lett, 5 (10): 1119-23. [PMID:25313323]

14. Uyttenhove C, Pilotte L, Théate I, Stroobant V, Colau D, Parmentier N, Boon T, Van den Eynde BJ. (2003) Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat. Med., 9 (10): 1269-74. [PMID:14502282]

15. Yang S, Li X, Hu F, Li Y, Yang Y, Yan J, Kuang C, Yang Q. (2013) Discovery of tryptanthrin derivatives as potent inhibitors of indoleamine 2,3-dioxygenase with therapeutic activity in Lewis lung cancer (LLC) tumor-bearing mice. J. Med. Chem., 56 (21): 8321-31. [PMID:24099220]

16. Yue EW, Douty B, Wayland B, Bower M, Liu X, Leffet L, Wang Q, Bowman KJ, Hansbury MJ, Liu C et al.. (2009) Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model. J. Med. Chem., 52 (23): 7364-7. [PMID:19507862]

How to cite this page

1.13.11.- Dioxygenases: indoleamine 2,3-dioxygenase 1. Last modified on 04/05/2018. Accessed on 20/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY,