Target General Infomation
Target ID
T89697 (Former ID: TTDS00476)
Target Name
Indoleamine 2,3-dioxygenase 1 (IDO1)
Synonyms
Indoleamine-pyrrole 2,3-dioxygenase; INDO; IDO-1; IDO
Gene Name
IDO1
Target Type
Successful target
[1]
Disease [+] 1 Target-related Diseases +
1 Depression [ICD-11: 6A70-6A7Z]
Function
Involved in the peripheral immune tolerance, contributing to maintain homeostasis by preventing autoimmunity or immunopathology that would result from uncontrolled and overreacting immune responses. Tryptophan shortage inhibits T lymphocytes division and accumulation of tryptophan catabolites induces T-cell apoptosis and differentiation of regulatory T-cells. Acts as a suppressor of anti-tumor immunity. Limits the growth of intracellular pathogens by depriving tryptophan. Protects the fetus from maternal immune rejection. Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway.
BioChemical Class
Oxygenase
UniProt ID
I23O1_HUMAN
EC Number
EC 1.13.11.52
Sequence
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL
PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV
IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN
PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP
PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ
QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG
Drugs and Modes of Action
Approved Drug(s) [+] 1 Approved Drugs +
1 L-Tryptophan Drug Info Approved Depression [2], [3]
Clinical Trial Drug(s) [+] 9 Clinical Trial Drugs +
1 Avastin+/-Tarceva Drug Info Phase 3 Non-small-cell lung cancer [4]
2 BMS-986205 Drug Info Phase 3 Melanoma [5], [6]
3 NLG8189 Drug Info Phase 2/3 Melanoma [5], [6]
4 Epacadostat Drug Info Phase 2 Melanoma [5], [6], [7]
5 INCB24360 Drug Info Phase 2 Solid tumour/cancer [8], [9]
6 KHK2455 Drug Info Phase 1 Solid tumour/cancer [5]
7 LY3381916 Drug Info Phase 1 Solid tumour/cancer [5]
8 NLG802 Drug Info Phase 1 Solid tumour/cancer [5]
9 PF-06840003 Drug Info Phase 1 Glioma [10]
Mode of Action [+] 4 Modes of Action +
Binder [+] 1 Binder drugs +
1 L-Tryptophan Drug Info [1]
Inhibitor [+] 144 Inhibitor drugs +
1 Avastin+/-Tarceva Drug Info [11]
2 BMS-986205 Drug Info [5], [6]
3 Epacadostat Drug Info [5], [6], [10]
4 NLG8189 Drug Info [5], [6]
5 INCB24360 Drug Info [12]
6 KHK2455 Drug Info [5]
7 LY3381916 Drug Info [5]
8 NLG802 Drug Info [5]
9 PF-06840003 Drug Info [10]
10 2,3-diamino-benzo[b]thiophene derivative 1 Drug Info [13]
11 2,3-diamino-benzo[b]thiophene derivative 2 Drug Info [13]
12 2,3-diamino-benzo[b]thiophene derivative 3 Drug Info [13]
13 2,3-diamino-benzo[b]thiophene derivative 4 Drug Info [13]
14 2,3-diamino-benzo[b]thiophene derivative 5 Drug Info [13]
15 2,3-diamino-benzo[b]thiophene derivative 6 Drug Info [13]
16 2,3-diamino-benzo[b]thiophene derivative 7 Drug Info [13]
17 2,3-diamino-benzo[b]thiophene derivative 8 Drug Info [13]
18 Acyl piperidine derivative 1 Drug Info [14]
19 Amide derivative 2 Drug Info [14]
20 Aryl 1,2-diamine derivative 1 Drug Info [14]
21 Aryl sulphoxide imine derivative 1 Drug Info [14]
22 Azetidine derivative 5 Drug Info [14]
23 Benzimidazole and imadazopyridine carboximidamide compound 1 Drug Info [14]
24 Benzimidazole and imadazopyridine carboximidamide compound 2 Drug Info [14]
25 Biphenyl derivative 1 Drug Info [14]
26 Biphenyl derivative 2 Drug Info [14]
27 Biphenyl derivative 3 Drug Info [14]
28 Carbamide derivative 13 Drug Info [14]
29 Cyclic hydroxamate derivative 1 Drug Info [14]
30 Five-membered heteroaromatic compound 1 Drug Info [14]
31 Five-membered heteroaromatic compound 2 Drug Info [14]
32 Five-membered heteroaromatic compound 3 Drug Info [14]
33 Hexahydro quinoline derivative 1 Drug Info [14]
34 Hydoxyamidine derivative 1 Drug Info [14]
35 Hydroxy amidine derivative 1 Drug Info [14]
36 Hydroxy amidine derivative 2 Drug Info [14]
37 Imidazo isoindole derivative 1 Drug Info [14]
38 Imidazoleisoindoles derivative 1 Drug Info [14]
39 Imidazoleisoindoles derivative 2 Drug Info [14]
40 Imidazo[1,5-a]pyridine derivative 1 Drug Info [14]
41 Imidazo[1,5-a]pyridine derivative 2 Drug Info [14]
42 Monoaryl-1,2-diamine derivative 1 Drug Info [14]
43 Monoaryl-1,2-diamine derivative 2 Drug Info [14]
44 PMID27172114-Compound-30 Drug Info [13]
45 PMID29473428-Compound-14 Drug Info [14]
46 PMID29473428-Compound-15 Drug Info [14]
47 PMID29473428-Compound-21 Drug Info [14]
48 PMID29473428-Compound-22 Drug Info [14]
49 PMID29473428-Compound-29 Drug Info [14]
50 PMID29473428-Compound-33 Drug Info [14]
51 PMID29473428-Compound-34 Drug Info [14]
52 PMID29473428-Compound-43 Drug Info [14]
53 PMID29473428-Compound-47 Drug Info [14]
54 PMID29473428-Compound-48 Drug Info [14]
55 PMID29473428-Compound-50 Drug Info [14]
56 PMID29473428-Compound-52 Drug Info [14]
57 PMID29473428-Compound-53 Drug Info [14]
58 PMID29473428-Compound-54 Drug Info [14]
59 PMID29473428-Compound-58 Drug Info [14]
60 PMID29473428-Compound-59 Drug Info [14]
61 PMID29473428-Compound-60 Drug Info [14]
62 PMID29473428-Compound-70 Drug Info [14]
63 PMID29473428-Compound-71 Drug Info [14]
64 PMID29473428-Compound-72 Drug Info [14]
65 PMID29473428-Compound-76 Drug Info [14]
66 PMID29473428-Compound-80 Drug Info [14]
67 Pyridine derivative 1 Drug Info [14]
68 Pyridino tricyclic compound 1 Drug Info [14]
69 Pyrrolo[1,2-c]pyrazole derivative 1 Drug Info [14]
70 Sulfamic acid ester derivative 1 Drug Info [14]
71 Sulfamoylamide derivative 1 Drug Info [14]
72 Sulfonamide derivative 6 Drug Info [14]
73 Sulfonamide derivative 7 Drug Info [14]
74 Sulfonamide derivative 8 Drug Info [14]
75 Thieno[2,3-c]pyridine derivative 1 Drug Info [14]
76 1,2-NAPHTHOQUINONE Drug Info [11]
77 1,4-Naphthoquinone Drug Info [11]
78 1-methyl-L-tryptophan Drug Info [15]
79 1H-indole-4,7-dione Drug Info [16]
80 2,2-dimethyl-2H-benzo[g]chromene-5,10-dione Drug Info [11]
81 2,3-dichloro-1,4-naphthoquinone Drug Info [11]
82 2,3-dihydrobenzo[d]thiazole-2-thiol Drug Info [17]
83 2,4-Dichlorobenzenemethanethiol Drug Info [18]
84 2-(1H-Imidazol-4-yl)benzene-1,3-diol Drug Info [19]
85 2-(1H-Imidazol-4-yl)phenol Drug Info [19]
86 2-Chlorobenzenemethanethiol Drug Info [18]
87 2-hydroxygarveatin E Drug Info [20]
88 2-HYDROXYGARVIN A Drug Info [20]
89 2-methoxy-1,4-naphthoquinone Drug Info [11]
90 3,4-Dichlorobenzenemethanethiol Drug Info [18]
91 3-(1H-Imidazol-4-yl)benzenethiol Drug Info [19]
92 3-(4H-Imidazol-4-yl)benzenethiol Drug Info [19]
93 4-(1H-1,2,3-triazol-5-yl)pyridine Drug Info [17]
94 4-(2-(diethylamino)ethylamino)-1-naphthol Drug Info [17]
95 4-(2-Hydroxyethoxy)-1-naphthol Drug Info [17]
96 4-(Benzylamino)-1-naphthol Drug Info [17]
97 4-(Cyclohexylamino)-1-naphthol Drug Info [17]
98 4-(ethylamino)naphthalen-1-ol Drug Info [17]
99 4-(Isopropylamino)-1-naphthol Drug Info [17]
100 4-(methylamino)naphthalen-1-ol Drug Info [17]
101 4-(Pent-3-ylamino)-1-naphthol Drug Info [17]
102 4-(propylamino)naphthalen-1-ol Drug Info [17]
103 4-(tert-butylamino)naphthalen-1-ol Drug Info [17]
104 4-amino-1,2,5-oxadiazole-3-carboximidamide Drug Info [21]
105 4-aminonaphthalen-1-ol Drug Info [17]
106 4-Chlorobenzenemethanethiol Drug Info [18]
107 4-Fluorobenzenemethanethiol Drug Info [18]
108 4-Methoxybenzenemethanethiol Drug Info [18]
109 4-methoxynaphthalen-1-amine Drug Info [17]
110 4-Methylbenzenemethanethiol Drug Info [18]
111 4-Phenylimidazole Drug Info [19]
112 4-phenylthiazole-2-thiol Drug Info [17]
113 5-(isopropylamino)quinolin-8-ol Drug Info [17]
114 5-aminoquinolin-8-ol Drug Info [17]
115 5-phenyl-1H-1,2,3-triazole Drug Info [17]
116 amg-1 Drug Info [22]
117 ANNULIN A Drug Info [20]
118 ANNULIN B Drug Info [20]
119 ANNULIN C Drug Info [20]
120 BENZENEMETHANETHIOL Drug Info [18]
121 BLV-0801 Drug Info [23]
122 Exiguamine A Drug Info [16]
123 EXIGUAMINE B Drug Info [24]
124 GARVEATIN A Drug Info [20]
125 Garveatin C Drug Info [20]
126 Garveatin E Drug Info [20]
127 N-[2-(Indol-3-yl)ethyl]-S-benzyl-dithiocarbamate Drug Info [25]
128 Naphthalene-1,4-diol Drug Info [17]
129 PMID24099220C5i Drug Info [15]
130 S-(2,4-Dichlorobenzyl)isothiourea hydrobromide Drug Info [18]
131 S-(2-Chlorobenzyl)isothiourea hydrochloride Drug Info [18]
132 S-(3,4-Dichlorobenzyl)isothiourea hydrochloride Drug Info [18]
133 S-(3-Chlorobenzyl)isothiourea hydrochloride Drug Info [18]
134 S-(4-Bromobenzyl)isothiourea hydrobromide Drug Info [18]
135 S-(4-Chlorobenzyl)isothiourea hydrochloride Drug Info [18]
136 S-(4-Cyanobenzyl)isothiourea hydrobromide Drug Info [18]
137 S-(4-Ethylbenzyl)isothiourea hydrochloride Drug Info [18]
138 S-(4-Fluorobenzyl)isothiourea hydrochloride Drug Info [18]
139 S-(4-Methoxybenzyl)isothiourea hydrochloride Drug Info [18]
140 S-(4-Methylbenzyl)isothiourea hydrochloride Drug Info [18]
141 S-(4-Nitrobenzyl)isothiourea hydrochloride Drug Info [18]
142 S-Benzyl-brassinin Drug Info [25]
143 Seco-exiguamine Drug Info [24]
144 tryptanthrin Drug Info [15]
Modulator [+] 3 Modulator drugs +
1 Biphenyl 1,2-diamine derivative 1 Drug Info [14]
2 Monoaryl-1,2-diamine derivative 3 Drug Info [14]
3 Monoaryl-1,2-diamine derivative 4 Drug Info [14]
Antagonist [+] 4 Antagonist drugs +
1 Cyclohexyl-ethyl-substituted diaza and triaza-tricyclic compound 1 Drug Info [14]
2 Monofluorine derivative 1 Drug Info [14]
3 PMID29473428-Compound-39 Drug Info [14]
4 PMID29473428-Compound-41 Drug Info [14]
Target Affiliated Biological Pathways
BioCyc [+] 5 BioCyc Pathways +
1 Superpathway of tryptophan utilization
2 Tryptophan degradation
3 L-kynurenine degradation
4 Tryptophan degradation to 2-amino-3-carboxymuconate semialdehyde
5 NAD de novo biosynthesis
KEGG Pathway [+] 3 KEGG Pathways +
1 Tryptophan metabolism
2 Metabolic pathways
3 African trypanosomiasis
NetPath Pathway [+] 3 NetPath Pathways +
1 TSLP Signaling Pathway
2 IL5 Signaling Pathway
3 TGF_beta_Receptor Signaling Pathway
Pathwhiz Pathway [+] 1 Pathwhiz Pathways +
1 Tryptophan Metabolism
Reactome [+] 1 Reactome Pathways +
1 Tryptophan catabolism
WikiPathways [+] 2 WikiPathways +
1 Tryptophan metabolism
2 Metabolism of amino acids and derivatives
Target-Related Models and Studies
Target Validation
References
REF 1 Interactions between nitric oxide and indoleamine 2,3-dioxygenase. Biochemistry. 2006 Jul 18;45(28):8527-38.
REF 2 URL: 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 3 Drug information of L-Tryptophan, 2008. eduDrugs.
REF 4 Clinical pipeline report, company report or official report of Roche.
REF 5 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 6 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 7 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 8 URL: 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 9 ClinicalTrials.gov (NCT01961115) INCB024360 and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma. U.S. National Institutes of Health.
REF 10 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
REF 11 Indoleamine 2,3-dioxygenase is the anticancer target for a novel series of potent naphthoquinone-based inhibitors. J Med Chem. 2008 Mar 27;51(6):1706-18.
REF 12 Incyte. Product Development Pipeline.
REF 13 Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
REF 14 A patent review of IDO1 inhibitors for cancer.Expert Opin Ther Pat. 2018 Apr;28(4):317-330.
REF 15 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. 2013 Nov 14;56(21):8321-31.
REF 16 Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A. J Med Chem. 2008 May 8;51(9):2634-7.
REF 17 Rational design of indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2010 Feb 11;53(3):1172-89.
REF 18 S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5126-9.
REF 19 Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J Med Chem. 2008 Aug 28;51(16):4968-77.
REF 20 Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata. J Nat Prod. 2006 Oct;69(10):1496-9.
REF 21 Discovery of potent competitive inhibitors of indoleamine 2,3-dioxygenase with in vivo pharmacodynamic activity and efficacy in a mouse melanoma mo... J Med Chem. 2009 Dec 10;52(23):7364-7.
REF 22 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. 2011 Dec;1814(12):1947-54.
REF 23 URL: 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 24 Biomimetic synthesis of the IDO inhibitors exiguamine A and B. Nat Chem Biol. 2008 Sep;4(9):535-7.
REF 25 Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2006 Jan 26;49(2):684-92.

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