Target Information

Target General Infomation
Target ID
T89697
Former ID
TTDS00476
Target Name
Indoleamine 2,3-dioxygenase
Gene Name
IDO1
Synonyms
INDO; IDO; Indoleamine-pyrrole 2,3-dioxygenase; IDO1
Target Type
Successful
Disease Cancer [ICD9: 140-229; ICD10: C00-C96]
Depression [ICD9: 311; ICD10: F30-F39]
Function
Catalyzes the cleavage of the pyrrol ring of tryptophan and incorporates both atoms of a molecule of oxygen.
BioChemical Class
Oxidoreductases acting on single donors
Target Validation
T89697
UniProt ID
P14902
EC Number
EC 1.13.11.52
Sequence
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL
PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV
IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN
PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP
PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ
QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG
Drugs and Mode of Action
Drug(s) L-Tryptophan Drug Info Approved Depression [1], [2]
INCB24360 Drug Info Phase 2 Cancer [3], [4]
Inhibitor 1,2-NAPHTHOQUINONE Drug Info [5]
1,4-naphtho-quinone Drug Info [5]
1-methyl-L-tryptophan Drug Info [6]
1H-indole-4,7-dione Drug Info [7]
2,2-dimethyl-2H-benzo[g]chromene-5,10-dione Drug Info [5]
2,3-dichloro-1,4-naphthoquinone Drug Info [5]
2,3-dihydrobenzo[d]thiazole-2-thiol Drug Info [8]
2,4-Dichlorobenzenemethanethiol Drug Info [9]
2-(1H-Imidazol-4-yl)benzene-1,3-diol Drug Info [10]
2-(1H-Imidazol-4-yl)phenol Drug Info [10]
2-Chlorobenzenemethanethiol Drug Info [9]
2-hydroxygarveatin E Drug Info [11]
2-HYDROXYGARVIN A Drug Info [11]
2-methoxy-1,4-naphthoquinone Drug Info [5]
3,4-Dichlorobenzenemethanethiol Drug Info [9]
3-(1H-Imidazol-4-yl)benzenethiol Drug Info [10]
3-(4H-Imidazol-4-yl)benzenethiol Drug Info [10]
4-(1H-1,2,3-triazol-5-yl)pyridine Drug Info [8]
4-(2-(diethylamino)ethylamino)-1-naphthol Drug Info [8]
4-(2-Hydroxyethoxy)-1-naphthol Drug Info [8]
4-(Benzylamino)-1-naphthol Drug Info [8]
4-(Cyclohexylamino)-1-naphthol Drug Info [8]
4-(ethylamino)naphthalen-1-ol Drug Info [8]
4-(Isopropylamino)-1-naphthol Drug Info [8]
4-(methylamino)naphthalen-1-ol Drug Info [8]
4-(Pent-3-ylamino)-1-naphthol Drug Info [8]
4-(propylamino)naphthalen-1-ol Drug Info [8]
4-(tert-butylamino)naphthalen-1-ol Drug Info [8]
4-amino-1,2,5-oxadiazole-3-carboximidamide Drug Info [12]
4-aminonaphthalen-1-ol Drug Info [8]
4-Chlorobenzenemethanethiol Drug Info [9]
4-Fluorobenzenemethanethiol Drug Info [9]
4-Methoxybenzenemethanethiol Drug Info [9]
4-methoxynaphthalen-1-amine Drug Info [8]
4-Methylbenzenemethanethiol Drug Info [9]
4-Phenylimidazole Drug Info [10]
4-phenylthiazole-2-thiol Drug Info [8]
5-(isopropylamino)quinolin-8-ol Drug Info [8]
5-aminoquinolin-8-ol Drug Info [8]
5-phenyl-1H-1,2,3-triazole Drug Info [8]
amg-1 Drug Info [13]
ANNULIN A Drug Info [11]
ANNULIN B Drug Info [11]
ANNULIN C Drug Info [11]
BENZENEMETHANETHIOL Drug Info [9]
BLV-0801 Drug Info [14]
compound 5i Drug Info [6]
Exiguamine A Drug Info [7]
EXIGUAMINE B Drug Info [15]
GARVEATIN A Drug Info [11]
Garveatin C Drug Info [11]
Garveatin E Drug Info [11]
INCB24360 Drug Info [16]
JUGLONE Drug Info [5]
N-[2-(Indol-3-yl)ethyl]-S-benzyl-dithiocarbamate Drug Info [17]
Naphthalene-1,4-diol Drug Info [8]
S-(2,4-Dichlorobenzyl)isothiourea hydrobromide Drug Info [9]
S-(2-Chlorobenzyl)isothiourea hydrochloride Drug Info [9]
S-(3,4-Dichlorobenzyl)isothiourea hydrochloride Drug Info [9]
S-(3-Chlorobenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Bromobenzyl)isothiourea hydrobromide Drug Info [9]
S-(4-Chlorobenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Cyanobenzyl)isothiourea hydrobromide Drug Info [9]
S-(4-Ethylbenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Fluorobenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Methoxybenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Methylbenzyl)isothiourea hydrochloride Drug Info [9]
S-(4-Nitrobenzyl)isothiourea hydrochloride Drug Info [9]
S-Benzyl-brassinin Drug Info [17]
Seco-exiguamine Drug Info [15]
tryptanthrin Drug Info [6]
Binder L-Tryptophan Drug Info [18]
Pathways
BioCyc Pathway Superpathway of tryptophan utilization
Tryptophan degradation
L-kynurenine degradation
Tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde
NAD de novo biosynthesis
KEGG Pathway Tryptophan metabolism
Metabolic pathways
African trypanosomiasis
NetPath Pathway TSLP Signaling Pathway
IL5 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
PathWhiz Pathway Tryptophan Metabolism
Reactome Tryptophan catabolism
WikiPathways Tryptophan metabolism
Metabolism of amino acids and derivatives
References
REF 1(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 717).
REF 2Drug information of L-Tryptophan, 2008. eduDrugs.
REF 3ClinicalTrials.gov (NCT01961115) INCB024360 and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma. U.S. National Institutes of Health.
REF 4(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8221).
REF 5J Med Chem. 2008 Mar 27;51(6):1706-18. Epub 2008 Mar 5.Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors.
REF 6Discovery 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. 2013 Nov 14;56(21):8321-31.
REF 7J Med Chem. 2008 May 8;51(9):2634-7. Epub 2008 Apr 8.Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A.
REF 8J Med Chem. 2010 Feb 11;53(3):1172-89.Rational design of indoleamine 2,3-dioxygenase inhibitors.
REF 9Bioorg Med Chem Lett. 2010 Sep 1;20(17):5126-9. Epub 2010 Jul 11.S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase.
REF 10J Med Chem. 2008 Aug 28;51(16):4968-77. Epub 2008 Jul 30.Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase.
REF 11J Nat Prod. 2006 Oct;69(10):1496-9.Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata.
REF 12J Med Chem. 2009 Dec 10;52(23):7364-7.Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma model.
REF 13Purification and kinetic characterization of human indoleamine 2,3-dioxygenases 1 and 2 (IDO1 and IDO2) and discovery of selective IDO1 inhibitors. Biochim Biophys Acta. 2011 Dec;1814(12):1947-54.
REF 14(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2829).
REF 15Nat Chem Biol. 2008 Sep;4(9):535-7.Biomimetic synthesis of the IDO inhibitors exiguamine A and B.
REF 16Incyte. Product Development Pipeline.
REF 17J Med Chem. 2006 Jan 26;49(2):684-92.Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors.
REF 18Interactions between nitric oxide and indoleamine 2,3-dioxygenase. Biochemistry. 2006 Jul 18;45(28):8527-38.

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