Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZJYKH)

DTT Name Indoleamine 2,3-dioxygenase 1 (IDO1)
Synonyms Indoleamine-pyrrole 2,3-dioxygenase; INDO; IDO-1; IDO
Gene Name IDO1
DTT Type
Successful target
 [1]
BioChemical Class
Oxygenase
UniProt ID
I23O1_HUMAN
TTD ID
T89697
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 1.13.11.52
Sequence
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL
PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV
IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN
PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP
PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ
QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG
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.
KEGG Pathway
Tryptophan metabolism (hsa00380 )
Metabolic pathways (hsa01100 )
African trypanosomiasis (hsa05143 )
Reactome Pathway
Tryptophan catabolism (R-HSA-71240 )
BioCyc Pathway
MetaCyc:HS05502-MON

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
1 Approved Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [1]
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11 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
Avastin+/-Tarceva DMA86FL Non-small-cell lung cancer 2C25.Y Phase 3 [2]
BMS-986205 DM3MAYQ Melanoma 2C30 Phase 3 [3]
INCB24360 DMIJGT9 Urothelial carcinoma 2C92.0 Phase 3 [4]
NLG8189 DM0798Z Melanoma 2C30 Phase 2/3 [3]
DN1406131 DMQFX8R Solid tumour/cancer 2A00-2F9Z Phase 1 [5]
HTI-1090 DMI4TEC Solid tumour/cancer 2A00-2F9Z Phase 1 [6]
KHK2455 DMLSUQ8 Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
LY3381916 DMONZ1L Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
MK-7162 DMBSXZ1 Solid tumour/cancer 2A00-2F9Z Phase 1 [7]
NLG802 DMP9J5V Solid tumour/cancer 2A00-2F9Z Phase 1 [3]
PF-06840003 DMOX6EJ Glioma 2A00.0 Phase 1 [8]
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⏷ Show the Full List of 11 Clinical Trial Drug(s)
82 Patented Agent(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2,3-diamino-benzo[b]thiophene derivative 1 DMD2KRW N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 2 DMDYXKT N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 3 DMR7QKL N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 4 DMEDFNC N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 5 DM05WXD N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 6 DMINE6V N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 7 DMQVMNJ N. A. N. A. Patented [9]
2,3-diamino-benzo[b]thiophene derivative 8 DM5O8K0 N. A. N. A. Patented [9]
Acyl piperidine derivative 1 DMX9J1C N. A. N. A. Patented [10]
Amide derivative 2 DMBKIR0 N. A. N. A. Patented [10]
Aryl 1,2-diamine derivative 1 DMSDRNQ N. A. N. A. Patented [10]
Aryl sulphoxide imine derivative 1 DMW7HKS N. A. N. A. Patented [10]
Azetidine derivative 5 DMJ9U0E N. A. N. A. Patented [10]
Benzimidazole and imadazopyridine carboximidamide compound 1 DM2G83R N. A. N. A. Patented [10]
Benzimidazole and imadazopyridine carboximidamide compound 2 DMJ2CIY N. A. N. A. Patented [10]
Biphenyl 1,2-diamine derivative 1 DM1VYZ9 N. A. N. A. Patented [10]
Biphenyl derivative 1 DMG4WQB N. A. N. A. Patented [10]
Biphenyl derivative 2 DMJ4TZX N. A. N. A. Patented [10]
Biphenyl derivative 3 DMM3SWV N. A. N. A. Patented [10]
Carbamide derivative 13 DMCAD64 N. A. N. A. Patented [10]
Cyclic hydroxamate derivative 1 DM0K62M N. A. N. A. Patented [10]
Cyclohexyl-ethyl-substituted diaza and triaza-tricyclic compound 1 DMI2T1D N. A. N. A. Patented [10]
Five-membered heteroaromatic compound 1 DMO8UKD N. A. N. A. Patented [10]
Five-membered heteroaromatic compound 2 DM1QH8Z N. A. N. A. Patented [10]
Five-membered heteroaromatic compound 3 DMS0P9E N. A. N. A. Patented [10]
Hexahydro quinoline derivative 1 DM4VNWX N. A. N. A. Patented [10]
Hydoxyamidine derivative 1 DMFIG8C N. A. N. A. Patented [10]
Hydroxy amidine derivative 1 DMBHIL2 N. A. N. A. Patented [10]
Hydroxy amidine derivative 2 DM7SUFJ N. A. N. A. Patented [10]
Imidazo isoindole derivative 1 DM1JXKY N. A. N. A. Patented [10]
Imidazoleisoindoles derivative 1 DM7UMW2 N. A. N. A. Patented [10]
Imidazoleisoindoles derivative 2 DMRJKIQ N. A. N. A. Patented [10]
Imidazo[1,5-a]pyridine derivative 1 DMFIP0D N. A. N. A. Patented [10]
Imidazo[1,5-a]pyridine derivative 2 DMU3PAR N. A. N. A. Patented [10]
Indazole derivative 2 DMV7AX9 N. A. N. A. Patented [10]
Indazole derivative 3 DMVUWLK N. A. N. A. Patented [10]
Indazole derivative 4 DMJ2CRO N. A. N. A. Patented [10]
Monoaryl-1,2-diamine derivative 1 DMCI6YH N. A. N. A. Patented [10]
Monoaryl-1,2-diamine derivative 2 DMXUNZ1 N. A. N. A. Patented [10]
Monoaryl-1,2-diamine derivative 3 DMAXKPC N. A. N. A. Patented [10]
Monoaryl-1,2-diamine derivative 4 DMD8AKH N. A. N. A. Patented [10]
Monofluorine derivative 1 DMJ8YZK N. A. N. A. Patented [10]
PMID27172114-Compound-30 DMBWLSA N. A. N. A. Patented [9]
PMID29473428-Compound-10 DM7EW5U N. A. N. A. Patented [10]
PMID29473428-Compound-11 DM5MXFK N. A. N. A. Patented [10]
PMID29473428-Compound-14 DMCB0D6 N. A. N. A. Patented [10]
PMID29473428-Compound-15 DM571JP N. A. N. A. Patented [10]
PMID29473428-Compound-16 DM21QCE N. A. N. A. Patented [10]
PMID29473428-Compound-17 DMI04GC N. A. N. A. Patented [10]
PMID29473428-Compound-21 DMZGNWO N. A. N. A. Patented [10]
PMID29473428-Compound-22 DMCNSZD N. A. N. A. Patented [10]
PMID29473428-Compound-29 DMBMTUV N. A. N. A. Patented [10]
PMID29473428-Compound-33 DMZA3FL N. A. N. A. Patented [10]
PMID29473428-Compound-34 DM7BRPI N. A. N. A. Patented [10]
PMID29473428-Compound-39 DMKRUPW N. A. N. A. Patented [10]
PMID29473428-Compound-4 DM9KVOD N. A. N. A. Patented [10]
PMID29473428-Compound-41 DM4AOIR N. A. N. A. Patented [10]
PMID29473428-Compound-43 DMQ8EYV N. A. N. A. Patented [10]
PMID29473428-Compound-47 DMCLJ0M N. A. N. A. Patented [10]
PMID29473428-Compound-48 DMAYT2E N. A. N. A. Patented [10]
PMID29473428-Compound-50 DMXUVDH N. A. N. A. Patented [10]
PMID29473428-Compound-52 DMSXKP6 N. A. N. A. Patented [10]
PMID29473428-Compound-53 DMOASLQ N. A. N. A. Patented [10]
PMID29473428-Compound-54 DMKIS26 N. A. N. A. Patented [10]
PMID29473428-Compound-58 DMVP7DL N. A. N. A. Patented [10]
PMID29473428-Compound-59 DMJYUN2 N. A. N. A. Patented [10]
PMID29473428-Compound-6 DMOVPWD N. A. N. A. Patented [10]
PMID29473428-Compound-60 DMRKWPQ N. A. N. A. Patented [10]
PMID29473428-Compound-70 DMMV5KI N. A. N. A. Patented [10]
PMID29473428-Compound-71 DML5G6D N. A. N. A. Patented [10]
PMID29473428-Compound-72 DMJOBUZ N. A. N. A. Patented [10]
PMID29473428-Compound-76 DM8PZ46 N. A. N. A. Patented [10]
PMID29473428-Compound-80 DM8VBU2 N. A. N. A. Patented [10]
Pyridine derivative 1 DMSGF8T N. A. N. A. Patented [10]
Pyridino tricyclic compound 1 DMKQFTY N. A. N. A. Patented [10]
Pyrrolo[1,2-c]pyrazole derivative 1 DM5RCW8 N. A. N. A. Patented [10]
Sulfamic acid ester derivative 1 DMQ0VK9 N. A. N. A. Patented [10]
Sulfamoylamide derivative 1 DMO7ZRW N. A. N. A. Patented [10]
Sulfonamide derivative 6 DMD51AV N. A. N. A. Patented [10]
Sulfonamide derivative 7 DMN5YUK N. A. N. A. Patented [10]
Sulfonamide derivative 8 DMOXIZC N. A. N. A. Patented [10]
Thieno[2,3-c]pyridine derivative 1 DMLUPV1 N. A. N. A. Patented [10]
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⏷ Show the Full List of 82 Patented Agent(s)
3 Preclinical Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1-methyl-L-tryptophan DMT8SFV Solid tumour/cancer 2A00-2F9Z Preclinical [11]
EPL-1410 DM5K17C Solid tumour/cancer 2A00-2F9Z Preclinical [12]
RG70099 DM7JH0K Solid tumour/cancer 2A00-2F9Z Preclinical [12]
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68 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
1,2-NAPHTHOQUINONE DMYXELH Discovery agent N.A. Investigative [2]
1,4-Naphthoquinone DMTCMH7 Discovery agent N.A. Investigative [2]
1H-indole-4,7-dione DMNDVMH Discovery agent N.A. Investigative [13]
2,2-dimethyl-2H-benzo[g]chromene-5,10-dione DMQYCFI Discovery agent N.A. Investigative [2]
2,3-dichloro-1,4-naphthoquinone DMPCGSD Discovery agent N.A. Investigative [2]
2,3-dihydrobenzo[d]thiazole-2-thiol DMUW94S Discovery agent N.A. Investigative [14]
2,4-Dichlorobenzenemethanethiol DMR5DYK Discovery agent N.A. Investigative [15]
2-(1H-Imidazol-4-yl)benzene-1,3-diol DM2PZ1B Discovery agent N.A. Investigative [16]
2-(1H-Imidazol-4-yl)phenol DM6MR82 Discovery agent N.A. Investigative [16]
2-Chlorobenzenemethanethiol DMI89RL Discovery agent N.A. Investigative [15]
2-hydroxygarveatin E DM5E1DC Discovery agent N.A. Investigative [17]
2-HYDROXYGARVIN A DMK96BL Discovery agent N.A. Investigative [17]
2-methoxy-1,4-naphthoquinone DMA5Q4T Discovery agent N.A. Investigative [2]
3,4-Dichlorobenzenemethanethiol DMN61Q5 Discovery agent N.A. Investigative [15]
3-(1H-Imidazol-4-yl)benzenethiol DMERZHK Discovery agent N.A. Investigative [16]
3-(4H-Imidazol-4-yl)benzenethiol DMPS1GW Discovery agent N.A. Investigative [16]
4-(1H-1,2,3-triazol-5-yl)pyridine DMFWVJI Discovery agent N.A. Investigative [14]
4-(2-(diethylamino)ethylamino)-1-naphthol DMRQ8T9 Discovery agent N.A. Investigative [14]
4-(2-Hydroxyethoxy)-1-naphthol DM17QG8 Discovery agent N.A. Investigative [14]
4-(Benzylamino)-1-naphthol DMF6S3X Discovery agent N.A. Investigative [14]
4-(Cyclohexylamino)-1-naphthol DMUOQN7 Discovery agent N.A. Investigative [14]
4-(ethylamino)naphthalen-1-ol DM14C9V Discovery agent N.A. Investigative [14]
4-(Isopropylamino)-1-naphthol DMJFSTX Discovery agent N.A. Investigative [14]
4-(methylamino)naphthalen-1-ol DMF3O10 Discovery agent N.A. Investigative [14]
4-(Pent-3-ylamino)-1-naphthol DMHIDY6 Discovery agent N.A. Investigative [14]
4-(propylamino)naphthalen-1-ol DMEAZFJ Discovery agent N.A. Investigative [14]
4-(tert-butylamino)naphthalen-1-ol DMU5A2B Discovery agent N.A. Investigative [14]
4-amino-1,2,5-oxadiazole-3-carboximidamide DMNXSM2 Discovery agent N.A. Investigative [18]
4-aminonaphthalen-1-ol DMIG82P Discovery agent N.A. Investigative [14]
4-Chlorobenzenemethanethiol DMKTSPM Discovery agent N.A. Investigative [15]
4-Fluorobenzenemethanethiol DMS6RHD Discovery agent N.A. Investigative [15]
4-Methoxybenzenemethanethiol DMVFLCM Discovery agent N.A. Investigative [15]
4-methoxynaphthalen-1-amine DMBS61O Discovery agent N.A. Investigative [14]
4-Methylbenzenemethanethiol DM3S2P8 Discovery agent N.A. Investigative [15]
4-Phenylimidazole DM5UNBW Discovery agent N.A. Investigative [16]
4-phenylthiazole-2-thiol DM3B1CE Discovery agent N.A. Investigative [14]
5-(isopropylamino)quinolin-8-ol DM45VRX Discovery agent N.A. Investigative [14]
5-aminoquinolin-8-ol DMIBHP5 Discovery agent N.A. Investigative [14]
5-phenyl-1H-1,2,3-triazole DMWF4HX Discovery agent N.A. Investigative [14]
amg-1 DMUONK5 Discovery agent N.A. Investigative [19]
ANNULIN A DM0RUQ8 Discovery agent N.A. Investigative [17]
ANNULIN B DMDQXJ2 Discovery agent N.A. Investigative [17]
ANNULIN C DMTYQDO Discovery agent N.A. Investigative [17]
BENZENEMETHANETHIOL DMK5QYW Discovery agent N.A. Investigative [15]
BLV-0801 DMGB9PN Solid tumour/cancer 2A00-2F9Z Investigative [20]
Exiguamine A DMMZH3Q Discovery agent N.A. Investigative [13]
EXIGUAMINE B DME1TGM Discovery agent N.A. Investigative [21]
GARVEATIN A DM7GX1S Discovery agent N.A. Investigative [17]
Garveatin C DMXNQ15 Discovery agent N.A. Investigative [17]
Garveatin E DMUFZ18 Discovery agent N.A. Investigative [17]
N-[2-(Indol-3-yl)ethyl]-S-benzyl-dithiocarbamate DMJ8W6F Discovery agent N.A. Investigative [22]
Naphthalene-1,4-diol DMOQ43W Discovery agent N.A. Investigative [14]
PMID24099220C5i DMWOHAE Discovery agent N.A. Investigative [11]
S-(2,4-Dichlorobenzyl)isothiourea hydrobromide DMO1R69 Discovery agent N.A. Investigative [15]
S-(2-Chlorobenzyl)isothiourea hydrochloride DMN62KP Discovery agent N.A. Investigative [15]
S-(3,4-Dichlorobenzyl)isothiourea hydrochloride DMNMCQJ Discovery agent N.A. Investigative [15]
S-(3-Chlorobenzyl)isothiourea hydrochloride DMNG6JB Discovery agent N.A. Investigative [15]
S-(4-Bromobenzyl)isothiourea hydrobromide DM0XDFG Discovery agent N.A. Investigative [15]
S-(4-Chlorobenzyl)isothiourea hydrochloride DMWJE2X Discovery agent N.A. Investigative [15]
S-(4-Cyanobenzyl)isothiourea hydrobromide DMYGULD Discovery agent N.A. Investigative [15]
S-(4-Ethylbenzyl)isothiourea hydrochloride DMNXDWV Discovery agent N.A. Investigative [15]
S-(4-Fluorobenzyl)isothiourea hydrochloride DM10MET Discovery agent N.A. Investigative [15]
S-(4-Methoxybenzyl)isothiourea hydrochloride DM4XWAU Discovery agent N.A. Investigative [15]
S-(4-Methylbenzyl)isothiourea hydrochloride DMAGLI8 Discovery agent N.A. Investigative [15]
S-(4-Nitrobenzyl)isothiourea hydrochloride DMYRBO0 Discovery agent N.A. Investigative [15]
S-Benzyl-brassinin DM2RLXF Discovery agent N.A. Investigative [22]
Seco-exiguamine DMY7IVZ Discovery agent N.A. Investigative [21]
tryptanthrin DMTRYCI Discovery agent N.A. Investigative [11]
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⏷ Show the Full List of 68 Investigative Drug(s)

The Drug-Metabolizing Enzyme (DME) Role of This DTT

DTT DME Name Indoleamine 2,3-dioxygenase 1 (IDO1) DME Info
Gene Name IDO1
2 Approved Drug(s) Metabolized by This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
L-Tryptophan DMIBH7M Depression 6A70-6A7Z Approved [23]
Melatonin DMKWFBT Depression 6A70-6A7Z Approved [24]
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References

1 Interactions between nitric oxide and indoleamine 2,3-dioxygenase. Biochemistry. 2006 Jul 18;45(28):8527-38.
2 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.
3 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
4 Incyte. Product Development Pipeline.
5 ClinicalTrials.gov (NCT03641794) Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers. U.S. National Institutes of Health.
6 Discovery of cyanopyridine scaffold as novel indoleamine-2,3-dioxygenase 1 (IDO1) inhibitors through virtual screening and preliminary hit optimisation. J Enzyme Inhib Med Chem. 2019 Dec;34(1):250-263.
7 ClinicalTrials.gov (NCT03364049) Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002). U.S. National Institutes of Health.
8 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
9 Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
10 A patent review of IDO1 inhibitors for cancer.Expert Opin Ther Pat. 2018 Apr;28(4):317-330.
11 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.
12 Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019 May;18(5):379-401.
13 Synthesis of indoleamine 2,3-dioxygenase inhibitory analogues of the sponge alkaloid exiguamine A. J Med Chem. 2008 May 8;51(9):2634-7.
14 Rational design of indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2010 Feb 11;53(3):1172-89.
15 S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5126-9.
16 Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J Med Chem. 2008 Aug 28;51(16):4968-77.
17 Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata. J Nat Prod. 2006 Oct;69(10):1496-9.
18 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.
19 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.
20 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).
21 Biomimetic synthesis of the IDO inhibitors exiguamine A and B. Nat Chem Biol. 2008 Sep;4(9):535-7.
22 Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2006 Jan 26;49(2):684-92.
23 Kynurenine pathway metabolites and enzymes involved in redox reactions. Neuropharmacology. 2017 Jan;112(Pt B):331-345.
24 Molecular evidence that melatonin is enzymatically oxidized in a different manner than tryptophan: investigations with both indoleamine 2,3-dioxygenase and myeloperoxidase. Biochem J. 2005 May 15;388(Pt 1):205-15.