Target Information
| Target General Information | Top | |||||
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| Target ID |
T89697
(Former ID: TTDS00476)
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| Target Name |
Indoleamine 2,3-dioxygenase 1 (IDO1)
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| Synonyms |
Indoleamine-pyrrole 2,3-dioxygenase; INDO; IDO-1; IDO
Click to Show/Hide
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| Gene Name |
IDO1
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| Target Type |
Successful target
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[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.
Click to Show/Hide
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| BioChemical Class |
Oxygenase
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| UniProt ID | ||||||
| EC Number |
EC 1.13.11.52
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| Sequence |
MAHAMENSWTISKEYHIDEEVGFALPNPQENLPDFYNDWMFIAKHLPDLIESGQLRERVE
KLNMLSIDHLTDHKSQRLARLVLGCITMAYVWGKGHGDVRKVLPRNIAVPYCQLSKKLEL PPILVYADCVLANWKKKDPNKPLTYENMDVLFSFRDGDCSKGFFLVSLLVEIAAASAIKV IPTVFKAMQMQERDTLLKALLEIASCLEKALQVFHQIHDHVNPKAFFSVLRIYLSGWKGN PQLSDGLVYEGFWEDPKEFAGGSAGQSSVFQCFDVLLGIQQTAGGGHAAQFLQDMRRYMP PAHRNFLCSLESNPSVREFVLSKGDAGLREAYDACVKALVSLRSYHLQIVTKYILIPASQ QPKENKTSEDPSKLEAKGTGGTDLMNFLKTVRSTTEKSLLKEG Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T68XO1 | |||||
| Drugs and Modes of Action | Top | |||||
|---|---|---|---|---|---|---|
| Approved Drug(s) | [+] 1 Approved Drugs | + | ||||
| 1 | L-Tryptophan | Drug Info | Approved | Depression | [2], [3] | |
| Clinical Trial Drug(s) | [+] 11 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 | INCB24360 | Drug Info | Phase 3 | Urothelial carcinoma | [7] | |
| 4 | NLG8189 | Drug Info | Phase 2/3 | Melanoma | [5], [6] | |
| 5 | DN1406131 | Drug Info | Phase 1 | Solid tumour/cancer | [8] | |
| 6 | HTI-1090 | Drug Info | Phase 1 | Solid tumour/cancer | [9] | |
| 7 | KHK2455 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 8 | LY3381916 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 9 | MK-7162 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 10 | NLG802 | Drug Info | Phase 1 | Solid tumour/cancer | [5] | |
| 11 | PF-06840003 | Drug Info | Phase 1 | Glioma | [10] | |
| Preclinical Drug(s) | [+] 3 Preclinical Drugs | + | ||||
| 1 | 1-methyl-L-tryptophan | Drug Info | Preclinical | Solid tumour/cancer | [11] | |
| 2 | EPL-1410 | Drug Info | Preclinical | Solid tumour/cancer | [11] | |
| 3 | RG70099 | Drug Info | Preclinical | Solid tumour/cancer | [11] | |
| Mode of Action | [+] 4 Modes of Action | + | ||||
| Binder | [+] 1 Binder drugs | + | ||||
| 1 | L-Tryptophan | Drug Info | [1] | |||
| Inhibitor | [+] 148 Inhibitor drugs | + | ||||
| 1 | Avastin+/-Tarceva | Drug Info | [12] | |||
| 2 | BMS-986205 | Drug Info | [5], [6] | |||
| 3 | INCB24360 | Drug Info | [13] | |||
| 4 | NLG8189 | Drug Info | [5], [6] | |||
| 5 | DN1406131 | Drug Info | [8] | |||
| 6 | HTI-1090 | Drug Info | [14] | |||
| 7 | KHK2455 | Drug Info | [5] | |||
| 8 | LY3381916 | Drug Info | [5] | |||
| 9 | MK-7162 | Drug Info | [15] | |||
| 10 | NLG802 | Drug Info | [5] | |||
| 11 | PF-06840003 | Drug Info | [10] | |||
| 12 | 2,3-diamino-benzo[b]thiophene derivative 1 | Drug Info | [16] | |||
| 13 | 2,3-diamino-benzo[b]thiophene derivative 2 | Drug Info | [16] | |||
| 14 | 2,3-diamino-benzo[b]thiophene derivative 3 | Drug Info | [16] | |||
| 15 | 2,3-diamino-benzo[b]thiophene derivative 4 | Drug Info | [16] | |||
| 16 | 2,3-diamino-benzo[b]thiophene derivative 5 | Drug Info | [16] | |||
| 17 | 2,3-diamino-benzo[b]thiophene derivative 6 | Drug Info | [16] | |||
| 18 | 2,3-diamino-benzo[b]thiophene derivative 7 | Drug Info | [16] | |||
| 19 | 2,3-diamino-benzo[b]thiophene derivative 8 | Drug Info | [16] | |||
| 20 | Acyl piperidine derivative 1 | Drug Info | [17] | |||
| 21 | Amide derivative 2 | Drug Info | [17] | |||
| 22 | Aryl 1,2-diamine derivative 1 | Drug Info | [17] | |||
| 23 | Aryl sulphoxide imine derivative 1 | Drug Info | [17] | |||
| 24 | Azetidine derivative 5 | Drug Info | [17] | |||
| 25 | Benzimidazole and imadazopyridine carboximidamide compound 1 | Drug Info | [17] | |||
| 26 | Benzimidazole and imadazopyridine carboximidamide compound 2 | Drug Info | [17] | |||
| 27 | Biphenyl derivative 1 | Drug Info | [17] | |||
| 28 | Biphenyl derivative 2 | Drug Info | [17] | |||
| 29 | Biphenyl derivative 3 | Drug Info | [17] | |||
| 30 | Carbamide derivative 13 | Drug Info | [17] | |||
| 31 | Cyclic hydroxamate derivative 1 | Drug Info | [17] | |||
| 32 | Five-membered heteroaromatic compound 1 | Drug Info | [17] | |||
| 33 | Five-membered heteroaromatic compound 2 | Drug Info | [17] | |||
| 34 | Five-membered heteroaromatic compound 3 | Drug Info | [17] | |||
| 35 | Hexahydro quinoline derivative 1 | Drug Info | [17] | |||
| 36 | Hydoxyamidine derivative 1 | Drug Info | [17] | |||
| 37 | Hydroxy amidine derivative 1 | Drug Info | [17] | |||
| 38 | Hydroxy amidine derivative 2 | Drug Info | [17] | |||
| 39 | Imidazo isoindole derivative 1 | Drug Info | [17] | |||
| 40 | Imidazoleisoindoles derivative 1 | Drug Info | [17] | |||
| 41 | Imidazoleisoindoles derivative 2 | Drug Info | [17] | |||
| 42 | Imidazo[1,5-a]pyridine derivative 1 | Drug Info | [17] | |||
| 43 | Imidazo[1,5-a]pyridine derivative 2 | Drug Info | [17] | |||
| 44 | Monoaryl-1,2-diamine derivative 1 | Drug Info | [17] | |||
| 45 | Monoaryl-1,2-diamine derivative 2 | Drug Info | [17] | |||
| 46 | PMID27172114-Compound-30 | Drug Info | [16] | |||
| 47 | PMID29473428-Compound-14 | Drug Info | [17] | |||
| 48 | PMID29473428-Compound-15 | Drug Info | [17] | |||
| 49 | PMID29473428-Compound-21 | Drug Info | [17] | |||
| 50 | PMID29473428-Compound-22 | Drug Info | [17] | |||
| 51 | PMID29473428-Compound-29 | Drug Info | [17] | |||
| 52 | PMID29473428-Compound-33 | Drug Info | [17] | |||
| 53 | PMID29473428-Compound-34 | Drug Info | [17] | |||
| 54 | PMID29473428-Compound-43 | Drug Info | [17] | |||
| 55 | PMID29473428-Compound-47 | Drug Info | [17] | |||
| 56 | PMID29473428-Compound-48 | Drug Info | [17] | |||
| 57 | PMID29473428-Compound-50 | Drug Info | [17] | |||
| 58 | PMID29473428-Compound-52 | Drug Info | [17] | |||
| 59 | PMID29473428-Compound-53 | Drug Info | [17] | |||
| 60 | PMID29473428-Compound-54 | Drug Info | [17] | |||
| 61 | PMID29473428-Compound-58 | Drug Info | [17] | |||
| 62 | PMID29473428-Compound-59 | Drug Info | [17] | |||
| 63 | PMID29473428-Compound-60 | Drug Info | [17] | |||
| 64 | PMID29473428-Compound-70 | Drug Info | [17] | |||
| 65 | PMID29473428-Compound-71 | Drug Info | [17] | |||
| 66 | PMID29473428-Compound-72 | Drug Info | [17] | |||
| 67 | PMID29473428-Compound-76 | Drug Info | [17] | |||
| 68 | PMID29473428-Compound-80 | Drug Info | [17] | |||
| 69 | Pyridine derivative 1 | Drug Info | [17] | |||
| 70 | Pyridino tricyclic compound 1 | Drug Info | [17] | |||
| 71 | Pyrrolo[1,2-c]pyrazole derivative 1 | Drug Info | [17] | |||
| 72 | Sulfamic acid ester derivative 1 | Drug Info | [17] | |||
| 73 | Sulfamoylamide derivative 1 | Drug Info | [17] | |||
| 74 | Sulfonamide derivative 6 | Drug Info | [17] | |||
| 75 | Sulfonamide derivative 7 | Drug Info | [17] | |||
| 76 | Sulfonamide derivative 8 | Drug Info | [17] | |||
| 77 | Thieno[2,3-c]pyridine derivative 1 | Drug Info | [17] | |||
| 78 | 1-methyl-L-tryptophan | Drug Info | [18] | |||
| 79 | EPL-1410 | Drug Info | [11] | |||
| 80 | RG70099 | Drug Info | [11] | |||
| 81 | 1,2-NAPHTHOQUINONE | Drug Info | [12] | |||
| 82 | 1,4-Naphthoquinone | Drug Info | [12] | |||
| 83 | 1H-indole-4,7-dione | Drug Info | [19] | |||
| 84 | 2,2-dimethyl-2H-benzo[g]chromene-5,10-dione | Drug Info | [12] | |||
| 85 | 2,3-dichloro-1,4-naphthoquinone | Drug Info | [12] | |||
| 86 | 2,3-dihydrobenzo[d]thiazole-2-thiol | Drug Info | [20] | |||
| 87 | 2,4-Dichlorobenzenemethanethiol | Drug Info | [21] | |||
| 88 | 2-(1H-Imidazol-4-yl)benzene-1,3-diol | Drug Info | [22] | |||
| 89 | 2-(1H-Imidazol-4-yl)phenol | Drug Info | [22] | |||
| 90 | 2-Chlorobenzenemethanethiol | Drug Info | [21] | |||
| 91 | 2-hydroxygarveatin E | Drug Info | [23] | |||
| 92 | 2-HYDROXYGARVIN A | Drug Info | [23] | |||
| 93 | 2-methoxy-1,4-naphthoquinone | Drug Info | [12] | |||
| 94 | 3,4-Dichlorobenzenemethanethiol | Drug Info | [21] | |||
| 95 | 3-(1H-Imidazol-4-yl)benzenethiol | Drug Info | [22] | |||
| 96 | 3-(4H-Imidazol-4-yl)benzenethiol | Drug Info | [22] | |||
| 97 | 4-(1H-1,2,3-triazol-5-yl)pyridine | Drug Info | [20] | |||
| 98 | 4-(2-(diethylamino)ethylamino)-1-naphthol | Drug Info | [20] | |||
| 99 | 4-(2-Hydroxyethoxy)-1-naphthol | Drug Info | [20] | |||
| 100 | 4-(Benzylamino)-1-naphthol | Drug Info | [20] | |||
| 101 | 4-(Cyclohexylamino)-1-naphthol | Drug Info | [20] | |||
| 102 | 4-(ethylamino)naphthalen-1-ol | Drug Info | [20] | |||
| 103 | 4-(Isopropylamino)-1-naphthol | Drug Info | [20] | |||
| 104 | 4-(methylamino)naphthalen-1-ol | Drug Info | [20] | |||
| 105 | 4-(Pent-3-ylamino)-1-naphthol | Drug Info | [20] | |||
| 106 | 4-(propylamino)naphthalen-1-ol | Drug Info | [20] | |||
| 107 | 4-(tert-butylamino)naphthalen-1-ol | Drug Info | [20] | |||
| 108 | 4-amino-1,2,5-oxadiazole-3-carboximidamide | Drug Info | [24] | |||
| 109 | 4-aminonaphthalen-1-ol | Drug Info | [20] | |||
| 110 | 4-Chlorobenzenemethanethiol | Drug Info | [21] | |||
| 111 | 4-Fluorobenzenemethanethiol | Drug Info | [21] | |||
| 112 | 4-Methoxybenzenemethanethiol | Drug Info | [21] | |||
| 113 | 4-methoxynaphthalen-1-amine | Drug Info | [20] | |||
| 114 | 4-Methylbenzenemethanethiol | Drug Info | [21] | |||
| 115 | 4-Phenylimidazole | Drug Info | [22] | |||
| 116 | 4-phenylthiazole-2-thiol | Drug Info | [20] | |||
| 117 | 5-(isopropylamino)quinolin-8-ol | Drug Info | [20] | |||
| 118 | 5-aminoquinolin-8-ol | Drug Info | [20] | |||
| 119 | 5-phenyl-1H-1,2,3-triazole | Drug Info | [20] | |||
| 120 | amg-1 | Drug Info | [25] | |||
| 121 | ANNULIN A | Drug Info | [23] | |||
| 122 | ANNULIN B | Drug Info | [23] | |||
| 123 | ANNULIN C | Drug Info | [23] | |||
| 124 | BENZENEMETHANETHIOL | Drug Info | [21] | |||
| 125 | BLV-0801 | Drug Info | [26] | |||
| 126 | Exiguamine A | Drug Info | [19] | |||
| 127 | EXIGUAMINE B | Drug Info | [27] | |||
| 128 | GARVEATIN A | Drug Info | [23] | |||
| 129 | Garveatin C | Drug Info | [23] | |||
| 130 | Garveatin E | Drug Info | [23] | |||
| 131 | N-[2-(Indol-3-yl)ethyl]-S-benzyl-dithiocarbamate | Drug Info | [28] | |||
| 132 | Naphthalene-1,4-diol | Drug Info | [20] | |||
| 133 | PMID24099220C5i | Drug Info | [18] | |||
| 134 | S-(2,4-Dichlorobenzyl)isothiourea hydrobromide | Drug Info | [21] | |||
| 135 | S-(2-Chlorobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 136 | S-(3,4-Dichlorobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 137 | S-(3-Chlorobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 138 | S-(4-Bromobenzyl)isothiourea hydrobromide | Drug Info | [21] | |||
| 139 | S-(4-Chlorobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 140 | S-(4-Cyanobenzyl)isothiourea hydrobromide | Drug Info | [21] | |||
| 141 | S-(4-Ethylbenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 142 | S-(4-Fluorobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 143 | S-(4-Methoxybenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 144 | S-(4-Methylbenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 145 | S-(4-Nitrobenzyl)isothiourea hydrochloride | Drug Info | [21] | |||
| 146 | S-Benzyl-brassinin | Drug Info | [28] | |||
| 147 | Seco-exiguamine | Drug Info | [27] | |||
| 148 | tryptanthrin | Drug Info | [18] | |||
| Modulator | [+] 3 Modulator drugs | + | ||||
| 1 | Biphenyl 1,2-diamine derivative 1 | Drug Info | [17] | |||
| 2 | Monoaryl-1,2-diamine derivative 3 | Drug Info | [17] | |||
| 3 | Monoaryl-1,2-diamine derivative 4 | Drug Info | [17] | |||
| Antagonist | [+] 4 Antagonist drugs | + | ||||
| 1 | Cyclohexyl-ethyl-substituted diaza and triaza-tricyclic compound 1 | Drug Info | [17] | |||
| 2 | Monofluorine derivative 1 | Drug Info | [17] | |||
| 3 | PMID29473428-Compound-39 | Drug Info | [17] | |||
| 4 | PMID29473428-Compound-41 | Drug Info | [17] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: L-alanine | Ligand Info | |||||
| Structure Description | Crystal structure of human indoleamine 2,3-dioxygenase bound to a triazole inhibitor and alanine molecule. | PDB:6F0A | ||||
| Method | X-ray diffraction | Resolution | 2.26 Å | Mutation | No | [29] |
| PDB Sequence |
ISKEYHIDEE
20 VGFALPNPQE30 NLPDFYNDWM40 FIAKHLPDLI50 ESGQLRERVE60 KLNMLSIDHL 70 TDHKSQRLAR80 LVLGCITMAY90 VWGKGHGDVR100 KVLPRNIAVP110 YCQLSKKLEL 120 PPILVYADCV130 LANWKKKDPN140 KPLTYENMDV150 LFSFRDGDCS160 KGFFLVSLLV 170 EIAAASAIKV180 IPTVFKAMQM190 QERDTLLKAL200 LEIASCLEKA210 LQVFHQIHDH 220 VNPKAFFSVL230 RIYLSGWKGN240 PQLSDGLVYE250 GFWEDPKEFA260 GGSAGQSSVF 270 QCFDVLLGIQ280 QTAGGGHAAQ290 FLQDMRRYMP300 PAHRNFLCSL310 ESNPSVREFV 320 LSKGDAGLRE330 AYDACVKALV340 SLRSYHLQIV350 TKYILIPASQ360 QPKLEAKGTG 380 GTDLMNFLKT390 VRSTTEKSLL400 KEG
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| Ligand Name: INCB24360 | Ligand Info | |||||
| Structure Description | Crystal structure of the indoleamine 2,3-dioxygenase 1 (IDO1) in complexed with ferric heme and Epacadostat | PDB:6E40 | ||||
| Method | X-ray diffraction | Resolution | 2.31 Å | Mutation | Yes | [30] |
| PDB Sequence |
AYHIDEEVGF
23 ALPNPQENLP33 DFYNDWMFIA43 KHLPDLIESG53 QLRERVEKLN63 MLSIDHLTDH 73 KSQRLARLVL83 GCITMAYVWG93 KGHGDVRKVL103 PRNIAVPYCQ113 LSAALELPPI 123 LVYADCVLAN133 WKKKDPNKPL143 TYENMDVLFS153 FRDGDCSKGF163 FLVSLLVEIA 173 AASAIKVIPT183 VFKAMQMQER193 DTLLKALLEI203 ASCLEKALQV213 FHQIHDHVNP 223 KAFFSVLRIY233 LSGWKGNPQL243 SDGLVYEGFW253 EDPKEFAGGS263 AGQSSVFQCF 273 DVLLGIQQTA283 GGGHAAQFLQ293 DMRRYMPPAH303 RNFLCSLESN313 PSVREFVLSK 323 GDAGLREAYD333 ACVKALVSLR343 SYHLQIVTKY353 ILIPASQGGT382 DLMNFLKTVR 392 STTEKSLLKE402
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Tryptophan metabolism | hsa00380 | Affiliated Target |
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| Class: Metabolism => Amino acid metabolism | Pathway Hierarchy | ||
| Degree | 2 | Degree centrality | 2.15E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.25E-01 | Radiality | 1.08E+01 | Clustering coefficient | 1.00E+00 |
| Neighborhood connectivity | 7.00E+00 | Topological coefficient | 7.00E-01 | Eccentricity | 13 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Co-Targets | Top | |||||
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| Co-Targets | ||||||
| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| 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 | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| 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 | ClinicalTrials.gov (NCT03361865) Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307). U.S. National Institutes of Health. | |||||
| REF 8 | ClinicalTrials.gov (NCT03641794) Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers. U.S. National Institutes of Health. | |||||
| REF 9 | ClinicalTrials.gov (NCT03208959) A Trial of HTI-1090 in Subjects With Advanced Solid Tumors. 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 | Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019 May;18(5):379-401. | |||||
| REF 12 | 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 13 | Incyte. Product Development Pipeline. | |||||
| REF 14 | 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. | |||||
| REF 15 | 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. | |||||
| REF 16 | Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32. | |||||
| REF 17 | A patent review of IDO1 inhibitors for cancer.Expert Opin Ther Pat. 2018 Apr;28(4):317-330. | |||||
| REF 18 | 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 19 | 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 20 | Rational design of indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2010 Feb 11;53(3):1172-89. | |||||
| REF 21 | S-benzylisothiourea derivatives as small-molecule inhibitors of indoleamine-2,3-dioxygenase. Bioorg Med Chem Lett. 2010 Sep 1;20(17):5126-9. | |||||
| REF 22 | Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. J Med Chem. 2008 Aug 28;51(16):4968-77. | |||||
| REF 23 | Indoleamine 2,3-dioxygenase inhibitors from the Northeastern Pacific Marine Hydroid Garveia annulata. J Nat Prod. 2006 Oct;69(10):1496-9. | |||||
| REF 24 | 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 25 | 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 26 | 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 27 | Biomimetic synthesis of the IDO inhibitors exiguamine A and B. Nat Chem Biol. 2008 Sep;4(9):535-7. | |||||
| REF 28 | Structure-activity study of brassinin derivatives as indoleamine 2,3-dioxygenase inhibitors. J Med Chem. 2006 Jan 26;49(2):684-92. | |||||
| REF 29 | New 4-Amino-1,2,3-Triazole Inhibitors of Indoleamine 2,3-Dioxygenase Form a Long-Lived Complex with the Enzyme and Display Exquisite Cellular Potency. Chembiochem. 2018 Mar 16;19(6):552-561. | |||||
| REF 30 | High-resolution structures of inhibitor complexes of human indoleamine 2,3-dioxygenase 1 in a new crystal form. Acta Crystallogr F Struct Biol Commun. 2018 Nov 1;74(Pt 11):717-724. | |||||
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