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 [542179], [552005]
INCB24360 Drug Info Phase 2 Cancer [524471], [543000]
Inhibitor 1,2-NAPHTHOQUINONE Drug Info [529353]
1,4-naphtho-quinone Drug Info [529353]
1-methyl-L-tryptophan Drug Info [532500]
1H-indole-4,7-dione Drug Info [529405]
2,2-dimethyl-2H-benzo[g]chromene-5,10-dione Drug Info [529353]
2,3-dichloro-1,4-naphthoquinone Drug Info [529353]
2,3-dihydrobenzo[d]thiazole-2-thiol Drug Info [530623]
2,4-Dichlorobenzenemethanethiol Drug Info [531087]
2-(1H-Imidazol-4-yl)benzene-1,3-diol Drug Info [529619]
2-(1H-Imidazol-4-yl)phenol Drug Info [529619]
2-Chlorobenzenemethanethiol Drug Info [531087]
2-hydroxygarveatin E Drug Info [528499]
2-HYDROXYGARVIN A Drug Info [528499]
2-methoxy-1,4-naphthoquinone Drug Info [529353]
3,4-Dichlorobenzenemethanethiol Drug Info [531087]
3-(1H-Imidazol-4-yl)benzenethiol Drug Info [529619]
3-(4H-Imidazol-4-yl)benzenethiol Drug Info [529619]
4-(1H-1,2,3-triazol-5-yl)pyridine Drug Info [530623]
4-(2-(diethylamino)ethylamino)-1-naphthol Drug Info [530623]
4-(2-Hydroxyethoxy)-1-naphthol Drug Info [530623]
4-(Benzylamino)-1-naphthol Drug Info [530623]
4-(Cyclohexylamino)-1-naphthol Drug Info [530623]
4-(ethylamino)naphthalen-1-ol Drug Info [530623]
4-(Isopropylamino)-1-naphthol Drug Info [530623]
4-(methylamino)naphthalen-1-ol Drug Info [530623]
4-(Pent-3-ylamino)-1-naphthol Drug Info [530623]
4-(propylamino)naphthalen-1-ol Drug Info [530623]
4-(tert-butylamino)naphthalen-1-ol Drug Info [530623]
4-amino-1,2,5-oxadiazole-3-carboximidamide Drug Info [530194]
4-aminonaphthalen-1-ol Drug Info [530623]
4-Chlorobenzenemethanethiol Drug Info [531087]
4-Fluorobenzenemethanethiol Drug Info [531087]
4-Methoxybenzenemethanethiol Drug Info [531087]
4-methoxynaphthalen-1-amine Drug Info [530623]
4-Methylbenzenemethanethiol Drug Info [531087]
4-Phenylimidazole Drug Info [529619]
4-phenylthiazole-2-thiol Drug Info [530623]
5-(isopropylamino)quinolin-8-ol Drug Info [530623]
5-aminoquinolin-8-ol Drug Info [530623]
5-phenyl-1H-1,2,3-triazole Drug Info [530623]
amg-1 Drug Info [531599]
ANNULIN A Drug Info [528499]
ANNULIN B Drug Info [528499]
ANNULIN C Drug Info [528499]
BENZENEMETHANETHIOL Drug Info [531087]
BLV-0801 Drug Info [543722]
compound 5i Drug Info [532500]
Exiguamine A Drug Info [529405]
EXIGUAMINE B Drug Info [529627]
GARVEATIN A Drug Info [528499]
Garveatin C Drug Info [528499]
Garveatin E Drug Info [528499]
INCB24360 Drug Info [551022]
JUGLONE Drug Info [529353]
N-[2-(Indol-3-yl)ethyl]-S-benzyl-dithiocarbamate Drug Info [527977]
Naphthalene-1,4-diol Drug Info [530623]
S-(2,4-Dichlorobenzyl)isothiourea hydrobromide Drug Info [531087]
S-(2-Chlorobenzyl)isothiourea hydrochloride Drug Info [531087]
S-(3,4-Dichlorobenzyl)isothiourea hydrochloride Drug Info [531087]
S-(3-Chlorobenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Bromobenzyl)isothiourea hydrobromide Drug Info [531087]
S-(4-Chlorobenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Cyanobenzyl)isothiourea hydrobromide Drug Info [531087]
S-(4-Ethylbenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Fluorobenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Methoxybenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Methylbenzyl)isothiourea hydrochloride Drug Info [531087]
S-(4-Nitrobenzyl)isothiourea hydrochloride Drug Info [531087]
S-Benzyl-brassinin Drug Info [527977]
Seco-exiguamine Drug Info [529627]
tryptanthrin Drug Info [532500]
Binder L-Tryptophan Drug Info [536247]
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 524471ClinicalTrials.gov (NCT01961115) INCB024360 and Vaccine Therapy in Treating Patients With Stage III-IV Melanoma. U.S. National Institutes of Health.
Ref 542179(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 543000(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 552005Drug information of L-Tryptophan, 2008. eduDrugs.
Ref 527977J Med Chem. 2006 Jan 26;49(2):684-92.Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors.
Ref 528499J Nat Prod. 2006 Oct;69(10):1496-9.Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata.
Ref 529353J 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 529405J 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 529619J 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 529627Nat Chem Biol. 2008 Sep;4(9):535-7.Biomimetic synthesis of the IDO inhibitors exiguamine A and B.
Ref 530194J 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 530623J Med Chem. 2010 Feb 11;53(3):1172-89.Rational design of indoleamine 2,3-dioxygenase inhibitors.
Ref 531087Bioorg 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 531599Purification 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 532500Discovery 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 536247Interactions between nitric oxide and indoleamine 2,3-dioxygenase. Biochemistry. 2006 Jul 18;45(28):8527-38.
Ref 543722(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 551022Incyte. Product Development Pipeline.

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