IDO1

Summary

IDO1 (indoleamine 2,3-dioxygenase 1, HGNC:6059) is a protein-coding gene on chromosome 8p11.21, encoding Indoleamine 2,3-dioxygenase 1 (P14902). Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway.

This gene encodes indoleamine 2,3-dioxygenase (IDO) - a heme enzyme that catalyzes the first and rate-limiting step in tryptophan catabolism to N-formyl-kynurenine. This enzyme acts on multiple tryptophan substrates including D-tryptophan, L-tryptophan, 5-hydroxy-tryptophan, tryptamine, and serotonin. This enzyme is thought to play a role in a variety of pathophysiological processes such as antimicrobial and antitumor defense, neuropathology, immunoregulation, and antioxidant activity. Through its expression in dendritic cells, monocytes, and macrophages this enzyme modulates T-cell behavior by its peri-cellular catabolization of the essential amino acid tryptophan.

Source: NCBI Gene 3620 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 74 total
• Druggable target: yes — 22 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002164

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6059
Approved symbol	IDO1
Name	indoleamine 2,3-dioxygenase 1
Location	8p11.21
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000131203
Ensembl biotype	protein_coding
OMIM	147435
Entrez	3620

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 5 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000253513, ENST00000518237, ENST00000518804, ENST00000519154, ENST00000521480, ENST00000521636, ENST00000522495, ENST00000522840, ENST00000523779

RefSeq mRNA: 1 — MANE Select: NM_002164 NM_002164

CCDS: CCDS47847

Canonical transcript exons

ENST00000518237 — 10 exons

Exon	Start	End
ENSE00000691700	39923469	39923586
ENSE00000900757	39917875	39917970
ENSE00002118048	39927830	39928790
ENSE00002133839	39913891	39914009
ENSE00003505182	39924721	39924772
ENSE00003577833	39922552	39922651
ENSE00003594230	39918815	39918933
ENSE00003622143	39920100	39920114
ENSE00003626133	39918088	39918207
ENSE00003678883	39925223	39925371

Expression profiles

Bgee: expression breadth ubiquitous, 175 present calls, max score 92.59.

FANTOM5 (CAGE): breadth broad, TPM avg 25.5777 / max 2707.6426, expressed in 335 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88592	21.7562	227
88591	1.6398	136
88588	1.1338	73
88590	0.9040	119
88589	0.1438	37

Top tissues by expression

285 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
palpebral conjunctiva	UBERON:0001812	92.59	gold quality
epithelium of nasopharynx	UBERON:0001951	92.40	gold quality
nasopharynx	UBERON:0001728	92.38	gold quality
vermiform appendix	UBERON:0001154	90.35	gold quality
nasal cavity epithelium	UBERON:0005384	90.16	gold quality
placenta	UBERON:0001987	87.59	gold quality
lymph node	UBERON:0000029	86.29	gold quality
endometrium	UBERON:0001295	85.53	gold quality
caecum	UBERON:0001153	83.18	gold quality
type B pancreatic cell	CL:0000169	82.81	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.93	gold quality
olfactory bulb	UBERON:0002264	80.90	gold quality
upper lobe of left lung	UBERON:0008952	80.39	gold quality
rectum	UBERON:0001052	79.41	gold quality
right lung	UBERON:0002167	79.26	gold quality
decidua	UBERON:0002450	78.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.24	gold quality
nasal cavity mucosa	UBERON:0001826	78.02	gold quality
upper lobe of lung	UBERON:0008948	77.80	gold quality
gall bladder	UBERON:0002110	77.02	gold quality
jejunal mucosa	UBERON:0000399	76.05	gold quality
lung	UBERON:0002048	75.71	gold quality
mucosa of transverse colon	UBERON:0004991	75.41	gold quality
thymus	UBERON:0002370	75.30	silver quality
superficial temporal artery	UBERON:0001614	75.23	gold quality
omental fat pad	UBERON:0010414	75.15	gold quality
peritoneum	UBERON:0002358	75.06	gold quality
duodenum	UBERON:0002114	74.65	gold quality
apex of heart	UBERON:0002098	74.37	gold quality
jejunum	UBERON:0002115	73.92	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 11.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	4335.25
E-MTAB-6505	yes	1910.67
E-GEOD-89232	yes	1759.73
E-CURD-95	yes	197.35
E-CURD-46	yes	25.97
E-HCAD-1	yes	23.99
E-MTAB-6701	yes	17.90
E-MTAB-8498	yes	10.97
E-CURD-88	yes	8.74
E-MTAB-6678	yes	8.14
E-MTAB-6524	no	169.87
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CTNNB1, EGR2, GLI2, IRF1, LEF1, PRDM1, PTMA, STAT1, ZNF699

miRNA regulators (miRDB)

18 targeting IDO1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-466	99.67	70.85	2863
HSA-MIR-586	99.65	70.40	2051
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-5689	99.50	71.26	1154
HSA-MIR-5683	99.36	68.59	2083
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-155-3P	99.03	67.99	924
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-760	98.81	66.65	1392
HSA-MIR-3161	98.71	67.14	816
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-4662A-5P	98.48	67.18	1007
HSA-MIR-10395-3P	98.10	66.70	1726
HSA-MIR-891A-3P	98.05	67.99	970
HSA-MIR-4474-3P	96.97	65.87	870

Literature-anchored findings (GeneRIF, showing 40)

• heme environment–structural properties and substrate-ligand interactions (PMID:11867636)
• Data show that overexpression of indoleamine-2,3-dioxygenase is present in Crohn’s disease as well as in ulcerative colitis, but nit in diverticulitis, as compared to normal mucosa. (PMID:11987129)
• inhibition of allogeneic T cell proliferation by indoleamine 2,3-dioxygenase-expressing dendritic cells: mediation of suppression by tryptophan metabolites (PMID:12186837)
• describe a subset of human monocyte-derived dendritic cells that use IDO to inhibit T cell proliferation in vitro (PMID:12228717)
• Induction of IDO in airway epithelial-like tumor cells by exposure to IFN-gamma for 24 hr markedly amplifies IL-6 and IL-8 responses via depletion of tryptophan from the culture medium. (PMID:12471139)
• Asp274 and his346 are essential for heme binding and catalytic function of human indoleamine 2,3-dioxygenase (PMID:12766158)
• Data show that indoleamine 2,3-dioxygenase-expressing fibroblasts embedded within collagen gel suppress the proliferation of allogenic immune cells, while they still remain viable in a tryptophan-deficient culture environment. (PMID:12938169)
• one important consequence of increasing IDO activity in astroglial cells during inflammation is to maintain NAD levels through de novo synthesis from tryptophan. (PMID:12963490)
• characterization of regulatory sequences involved in the synergistic transcriptional activation of the indoleamine dioxygenase gene by interferon-gamma and tumor necrosis factor-alpha. (PMID:13678429)
• Data show that most human tumors constitutively express indoleamine 2,3-dioxygenase (IDO), and that expression of IDO by immunogenic mouse tumor cells prevents their rejection by preimmunized mice. (PMID:14502282)
• indoleamine 2,3-dioxygenase is necessary for cytolytic activity of natural killer cells. (PMID:14871294)
• Downregulation of MHC class I expression by Indoleamine 2,3-dioxygenase(IDO) might be one of the mechanisms through which IDO mediates local immunosuppression. (PMID:14969766)
• Bone marrow stromal cells express IDO protein and exhibit functional IDO activity upon stimulation with IFN-gamma. (PMID:15001472)
• despite suppression by progesterone, indoleamine 2,3-dioxygenase expression in endometrial stromal cells may increase during decidualization due to stimulation by interferon-gamma secreted by infiltrating leukocytes. (PMID:15070879)
• RT4 cells were able to inhibit the growth of Staphylococcus aureus in an IDO-mediated fashion, and this bacteriostatic effect was abolished by endogenously produced NO. (PMID:15102781)
• stimulation with interferon-gamma (IFN-gamma) induces the expression of functionally active IDO in highly purified human epidermal Langerhans cells (PMID:15245429)
• Data suggest that indoleamine 2,3-dioxygenase-mediated suppression by plasmacytoid dendritic cells in tumor-draining lymph nodes creates a local microenvironment that is potently suppressive of host antitumor T cell responses. (PMID:15254595)
• HSV-2 antiviral effect of type II interferon and TNF-alpha is dependent on IDO activation. (PMID:15374002)
• IDO induction in eosinophils is a potential mechanism in the regulation of T helper type 2 (Th2) cell polarization. (PMID:15528322)
• Findings indicate that attenuated Bin1 causes elevation of IDO and immune escape of cancers in mice. Additionally, small molecule inhibitors of IDO reverse the effects of Bin1 loss and leverage the efficacy of chemotherapeutic drugs in cancer. (PMID:15711557)
• IFN-gamma-induced enzyme IDO plays an important antiviral role in Measles Virus infections of epithelial, endothelial, and astroglial cells. (PMID:15919929)
• indoleamine 2,3 dioxygenase (IDO) activity is induced in a two-step process during dendritic cell maturation (PMID:15947091)
• the function of IDO and kynurenine hydroxylase may change from a role in immunosuppression at the maternal-fetal interface in early pregnancy, to one associated with regulation of fetoplacental blood flow or placental metabolism in late gestation (PMID:15950064)
• Indoleamine 2,3-dioxygenase is expressed not by tumor cells, but by normal cells infiltrating the peritumoral stroma (PMID:15967116)
• A high T-helper type 1 (Th1)/Th2 cell ratio is more likely to cause loss of an allogeneic embryo in early pregnancy than is the loss of putative protection by reduced uterine levels of IDO. (PMID:16135011)
• In this review, the unique catalytic properties of indoleamine 2,3-dioxygenase are described, and the recent findings regarding the dioxygenase-initiated tryptophan metabolism are summarized. (PMID:16176799)
• HO-1/IDO cross-regulation modulates apoptosis and proliferation in rat and human breast cancer cells (PMID:16319139)
• examine the arguments for and against a function of IDO-expressing human dendritic cells (DCs) and conclude that proof for an immunoregulatory role in vivo is still lacking (PMID:16406698)
• CTLA-4 on regulatory T cells up-regulates IDO expression on decidual and peripheral blood dendritic cells and monocytes by the induction of IFN-gamma production. (PMID:16421220)
• X-ray crystal structure of human IDO, complexed with the ligand inhibitor 4-phenylimidazole and cyanide was reported. (PMID:16477023)
• IDO significantly contributes to disease progression and overall survival in patients with colorectal cancer. (PMID:16489067)
• purification, crystallization and preliminary X-ray study of human IDO (PMID:16511306)
• Indoleamine 2,3-dioxygenase may have a role in the decline of T cell responses in immunosenescence (PMID:16513157)
• The variable expression of IDO in different endothelial cells is important not only in understanding the role of endothelial cells in the regulation of graft rejection, but also as a potential therapeutic strategy. (PMID:16686756)
• These data provide the first glimpse of the possible regulatory mechanism of hIDO by NO and suggest that the NO-dependent regulation can be modulated by cellular factors, such as the NO abundance, pH, redox environment, and L-Trp availability. (PMID:16834326)
• reduced IDO activity found in the macrophages of patients with hepatitis C virus infection suggest the infection may hamper macrophage functions (PMID:16842443)
• Sleeping beuaty-bsed human indoleamine 2,3-dioxygenase represents a new strategy for treating lung transplantation-associated chronic complications in rats. (PMID:17015408)
• Recombinant antithymocyte globulin inhibits maturation of immature dendritic cells and llows the generation of dendritic cells expressing indoleamine 2,3-dioxygenase. (PMID:17038913)
• Acute myelocytic leukemia cells expresse INDO mRNA, but not IDO protein when exposed to optimal concentrations of IFN-gamma. (PMID:17170728)
• hCG can upregulate human trophoblast indoleamine 2, 3-dioxygenase, which probably plays a key role at maternal fetal interface in preventing fetal rejection. (PMID:17182891)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ido1	ENSMUSG00000031551
rattus_norvegicus	Ido1	ENSRNOG00000031189

Protein

Protein identifiers

Indoleamine 2,3-dioxygenase 1 — P14902 (reviewed: P14902)

Alternative names: Indoleamine-pyrrole 2,3-dioxygenase

All UniProt accessions (6): A0A140T9Z2, A0A348GSI3, E5RH36, E5RIX2, P14902, J3KN03

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the first and rate limiting step of the catabolism of the essential amino acid tryptophan along the kynurenine pathway. 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.

Subunit / interactions. Monomer.

Subcellular location. Cytoplasm. Cytosol.

Tissue specificity. Expressed in mature dendritic cells located in lymphoid organs (including lymph nodes, spleen, tonsils, Peyers’s patches, the gut lamina propria, and the thymic medulla), in some epithelial cells of the female genital tract, as well as in endothelial cells of term placenta and in lung parenchyma. Weakly or not expressed in most normal tissues, but mostly inducible in most tissues. Expressed in more than 50% of tumors, either by tumoral, stromal, or endothelial cells (expression in tumor is associated with a worse clinical outcome). Not overexpressed in tumor-draining lymph nodes.

Activity regulation. Activity is inhibited by and MTH-trp (methylthiohydantoin-DL-tryptophan), modestly inhibited by L-1MT (1-methyl-L-tryptophan) but not D-1MT (1-methyl-D-tryptophan).

Cofactor. Binds 1 heme group per subunit. In the active form, the heme iron is in its ferrous state Fe(+2). The catalytic cycle does not alter the oxidation state of the heme, but IDO1 is prone to autoxidation.

Induction. By IFNG/IFN-gamma in most cells. Exogenous inflammatory stimuli induce the expression of IDO1 in antigen-presenting cells such as dendritic cells, macrophages and B-cells.

Pathway. Amino-acid degradation; L-tryptophan degradation via kynurenine pathway; L-kynurenine from L-tryptophan: step 1/2.

Miscellaneous. IDO1 is the target for therapy in a range of clinical settings, including cancer, chronic infections, autoimmune and allergic syndromes, and transplantation. IDO1 and IDO2 are 2 distinct enzymes which catalyze the same reaction. IDO2 affinity for tryptophan is much lower than that of IDO1. 50% of Caucasians harbor polymorphisms which abolish IDO2 enzymatic activity. IDO2 is expressed in human tumors in an inactive form: tryptophan degradation is entirely provided by IDO1 in these cells. IDO2 may play a role as a negative regulator of IDO1 by competing for heme-binding with IDO1. Low efficiency IDO2 enzymes have been conserved throughout vertebrate evolution, whereas higher efficiency IDO1 enzymes are dispensable in many lower vertebrate lineages. IDO1 may have arisen by gene duplication of a more ancient proto-IDO gene before the divergence of marsupial and eutherian (placental) mammals. Elevated IDO1 expression is a hallmark of major viral infections including HIV, HBV, HCV or influenza and also of major bacteria infections, such as Tb, CAP, listeriosis and sepsis. Depletion of tryptophan and production of tryptophan metabolites with bactericidal activity are important as direct anti-pathogen mechanisms. Pathogens are able to highjack the immunosuppressive effects of IDO1 and make use of them to facilitate their own life cycle.

Similarity. Belongs to the indoleamine 2,3-dioxygenase family.

RefSeq proteins (1): NP_002155* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000898	Indolamine_dOase	Family
IPR037217	Trp/Indoleamine_2_3_dOase-like	Homologous_superfamily

Pfam: PF01231

Enzyme classification (BRENDA):

• EC 1.13.11.11 — tryptophan 2,3-dioxygenase (BRENDA: 16 organisms, 15 substrates, 146 inhibitors, 17 Km, 8 kcat entries)
• EC 1.13.11.52 — indoleamine 2,3-dioxygenase (BRENDA: 49 organisms, 208 substrates, 831 inhibitors, 203 Km, 109 kcat entries)

Substrate kinetics (BRENDA)

23 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-TRYPTOPHAN	0.0007–62.4	96
D-TRYPTOPHAN	0.0019–16	27
L-TRYPTOPHAN	0.02–1.531	13
L-TRP	0.02–133	12
5-HYDROXY-L-TRYPTOPHAN	0.017–0.68	10
O2	0.037–119	10
5-FLUORO-DL-TRYPTOPHAN	0.006–100	6
5-METHYL-DL-TRYPTOPHAN	0.088–1.57	6
6-METHYL-DL-TRYPTOPHAN	0.056–3.457	5
D-TRP	0.3–5.2	5
6-FLUORO-DL-TRYPTOPHAN	0.186–186	4
1-METHYL-L-TRYPTOPHAN	0.062–0.696	3
1-METHYL-D-TRYPTOPHAN	0.66–0.747	2
5-FLUORO-TRYPTOPHAN	0.006–0.36	2
5-METHOXY-DL-TRYPTOPHAN	0.113–0.547	2

Catalyzed reactions (Rhea), 2 shown:

• D-tryptophan + O2 = N-formyl-D-kynurenine (RHEA:14189)
• L-tryptophan + O2 = N-formyl-L-kynurenine (RHEA:24536)

UniProt features (53 total): helix 27, strand 14, turn 6, chain 1, region of interest 1, compositionally biased region 1, binding site 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

85 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9FOH	X-RAY DIFFRACTION	1.6
8ABX	X-RAY DIFFRACTION	1.65
9F5R	X-RAY DIFFRACTION	1.69
9FOZ	X-RAY DIFFRACTION	1.69
6E43	X-RAY DIFFRACTION	1.71
6V52	X-RAY DIFFRACTION	1.78
9EW0	X-RAY DIFFRACTION	1.8
9S1V	X-RAY DIFFRACTION	1.85
6E44	X-RAY DIFFRACTION	1.9
6WJY	X-RAY DIFFRACTION	1.91
9ESC	X-RAY DIFFRACTION	1.95
4U72	X-RAY DIFFRACTION	2
6E45	X-RAY DIFFRACTION	2
9S1U	X-RAY DIFFRACTION	2
9S1X	X-RAY DIFFRACTION	2
6E46	X-RAY DIFFRACTION	2.09
9RIS	X-RAY DIFFRACTION	2.1
9S1W	X-RAY DIFFRACTION	2.1
6E42	X-RAY DIFFRACTION	2.1
7E0T	X-RAY DIFFRACTION	2.14
8U5I	X-RAY DIFFRACTION	2.17
7RRC	X-RAY DIFFRACTION	2.18
5EK3	X-RAY DIFFRACTION	2.21
6KPS	X-RAY DIFFRACTION	2.25
9ESB	X-RAY DIFFRACTION	2.25
6F0A	X-RAY DIFFRACTION	2.26
6KOF	X-RAY DIFFRACTION	2.26
7E0U	X-RAY DIFFRACTION	2.28
5WHR	X-RAY DIFFRACTION	2.28
8FUR	X-RAY DIFFRACTION	2.29

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P14902-F1	93.40	0.88

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (1): 346 (proximal binding residue)

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-71240	Tryptophan catabolism

MSigDB gene sets: 361 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GOBP_REGULATION_OF_CELL_ACTIVATION, LI_CISPLATIN_RESISTANCE_DN, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_BEHAVIOR, GOBP_TOLERANCE_INDUCTION, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_PROLIFERATION, GOBP_ALPHA_AMINO_ACID_METABOLIC_PROCESS, REACTOME_TRYPTOPHAN_CATABOLISM, GOBP_REGULATION_OF_LYMPHOCYTE_APOPTOTIC_PROCESS

GO Biological Process (22): positive regulation of T cell tolerance induction (GO:0002666), positive regulation of chronic inflammatory response (GO:0002678), positive regulation of type 2 immune response (GO:0002830), L-tryptophan catabolic process (GO:0006569), inflammatory response (GO:0006954), female pregnancy (GO:0007565), obsolete L-tryptophan catabolic process to L-kynurenine (GO:0019441), quinolinate biosynthetic process (GO:0019805), response to lipopolysaccharide (GO:0032496), negative regulation of interleukin-10 production (GO:0032693), positive regulation of interleukin-12 production (GO:0032735), multicellular organismal response to stress (GO:0033555), kynurenic acid biosynthetic process (GO:0034276), ‘de novo’ NAD+ biosynthetic process from L-tryptophan (GO:0034354), swimming behavior (GO:0036269), T cell proliferation (GO:0042098), negative regulation of T cell proliferation (GO:0042130), negative regulation of T cell apoptotic process (GO:0070233), positive regulation of T cell apoptotic process (GO:0070234), immune system process (GO:0002376), positive regulation of apoptotic process (GO:0043065), negative regulation of activated T cell proliferation (GO:0046007)

GO Molecular Function (8): L-tryptophan 2,3-dioxygenase activity (GO:0004833), electron transfer activity (GO:0009055), heme binding (GO:0020037), indoleamine 2,3-dioxygenase activity (GO:0033754), metal ion binding (GO:0046872), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen (GO:0016702), dioxygenase activity (GO:0051213)

GO Cellular Component (4): cytoplasm (GO:0005737), cytosol (GO:0005829), smooth muscle contractile fiber (GO:0030485), stereocilium bundle (GO:0032421)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of amino acids and derivatives	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
T cell apoptotic process	2
regulation of T cell apoptotic process	2
oxidoreductase activity, acting on single donors with incorporation of molecular oxygen, incorporation of two atoms of oxygen	2
cellular anatomical structure	2
T cell tolerance induction	1
positive regulation of tolerance induction	1
regulation of T cell tolerance induction	1
chronic inflammatory response	1
regulation of chronic inflammatory response	1
positive regulation of inflammatory response	1
regulation of type 2 immune response	1
type 2 immune response	1
positive regulation of immune response	1
aromatic amino acid catabolic process	1
indole-containing compound catabolic process	1
L-amino acid catabolic process	1
proteinogenic amino acid catabolic process	1
defense response	1
multi-organism reproductive process	1
multi-multicellular organism process	1
dicarboxylic acid biosynthetic process	1
quinolinate metabolic process	1
pyridine-containing compound biosynthetic process	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
negative regulation of cytokine production	1
interleukin-10 production	1
regulation of interleukin-10 production	1
positive regulation of cytokine production	1
interleukin-12 production	1
regulation of interleukin-12 production	1
response to stress	1
multicellular organismal process	1
kynurenic acid metabolic process	1
monocarboxylic acid biosynthetic process	1
aromatic amino acid metabolic process	1
NAD+ biosynthetic process	1
indole-containing compound metabolic process	1
L-amino acid metabolic process	1

Protein interactions and networks

STRING

2888 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IDO1	IFNG	P01579	920
IDO1	TDO2	P48775	907
IDO1	CTLA4	P16410	901
IDO1	CD274	Q9NZQ7	880
IDO1	FOXP3	Q9BZS1	876
IDO1	CD4	P01730	870
IDO1	TNFRSF18	Q9Y5U5	864
IDO1	IL10	P22301	855
IDO1	CD80	P33681	841
IDO1	KMO	O15229	815
IDO1	TNFRSF9	Q07011	814
IDO1	TNFSF18	Q9UNG2	813
IDO1	KYNU	Q16719	810
IDO1	CD8A	P01732	801
IDO1	IL2	P01585	798

IntAct

8 interactions, top by confidence:

A	B	Type	Score
IDO1	TERF2IP	psi-mi:“MI:0915”(physical association)	0.370
IDO1	htpG	psi-mi:“MI:0915”(physical association)	0.370
IDO1		psi-mi:“MI:0915”(physical association)	0.370
IDO1	MAN2B1	psi-mi:“MI:0914”(association)	0.350
IDO1		psi-mi:“MI:0915”(physical association)	0.000
PPP1R16A	IDO1	psi-mi:“MI:0915”(physical association)	0.000
DDX24	IDO1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): IDO1 (Two-hybrid), IDO1 (Two-hybrid), IDO1 (Two-hybrid), VSIG8 (Affinity Capture-MS), MAN2B1 (Affinity Capture-MS), IDO1 (Cross-Linking-MS (XL-MS)), IDO1 (Two-hybrid), APP (Reconstituted Complex)

ESM2 similar proteins: A0A140JWS8, A0A1D5AG16, A0A1L9WLI9, A0A1U8QK63, A0A2I1C3U2, A0A2I2F272, A0A411PQN8, A0A5B8YWJ9, A0A6G9KIF9, A0A823A8X6, A0A823AAW6, A1D8I8, A9XLE1, B4FNK8, C5FM58, C8VJQ1, E4V2N3, I1R9A6, I1S489, M1VV66, M1WG92, M2XHU6, O81395, P0DUR8, P14902, P28776, P46580, P47125, P51537, P51820, P91133, Q00681, Q00706, Q01966, Q0CG33, Q27783, Q27793, Q5AV07, Q5B7V0, Q5F495

Diamond homologs: A0A2I2F272, A0A6G9KIF9, A0A823AAW6, F1LV46, P0DUR8, P14902, P28776, P47125, P51537, Q0CG33, Q6ZQW0, Q8R0V5, Q9ERD9, Q01966

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

74 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	51
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1536 predictions. Top by Δscore:

Variant	Effect	Δscore
8:39902444:GAAGG:G	donor_gain	1.0000
8:39902447:GG:G	donor_gain	1.0000
8:39902448:GG:G	donor_gain	1.0000
8:39917872:A:AG	acceptor_gain	1.0000
8:39917872:AAG:A	acceptor_gain	1.0000
8:39917873:A:G	acceptor_gain	1.0000
8:39917963:T:G	donor_gain	1.0000
8:39918086:A:AG	acceptor_gain	1.0000
8:39918087:G:GA	acceptor_gain	1.0000
8:39918087:GTTA:G	acceptor_gain	1.0000
8:39918087:GTTAA:G	acceptor_gain	1.0000
8:39918934:G:GG	donor_gain	1.0000
8:39920066:A:AG	acceptor_gain	1.0000
8:39920066:AATT:A	acceptor_gain	1.0000
8:39920066:AATTG:A	acceptor_gain	1.0000
8:39920067:A:G	acceptor_gain	1.0000
8:39920067:ATT:A	acceptor_gain	1.0000
8:39920069:T:TA	acceptor_gain	1.0000
8:39922541:A:AG	acceptor_gain	1.0000
8:39922650:AA:A	donor_gain	1.0000
8:39922650:AAGT:A	donor_loss	1.0000
8:39922652:G:GG	donor_gain	1.0000
8:39923463:TTTTA:T	acceptor_loss	1.0000
8:39923464:TTTA:T	acceptor_loss	1.0000
8:39923465:TTA:T	acceptor_loss	1.0000
8:39923467:A:T	acceptor_loss	1.0000
8:39923468:G:GA	acceptor_loss	1.0000
8:39923591:GTGTT:G	donor_gain	1.0000
8:39925217:T:TA	acceptor_gain	1.0000
8:39925221:A:AG	acceptor_gain	1.0000

AlphaMissense

2650 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:39925224:T:A	W237R	0.988
8:39925224:T:C	W237R	0.988
8:39922601:T:C	F163L	0.987
8:39922603:C:A	F163L	0.987
8:39922603:C:G	F163L	0.987
8:39918819:T:C	L103S	0.986
8:39925317:A:C	S268R	0.986
8:39925319:C:A	S268R	0.986
8:39925319:C:G	S268R	0.986
8:39913989:T:C	F23L	0.985
8:39913991:T:A	F23L	0.985
8:39913991:T:G	F23L	0.985
8:39918834:C:A	A108D	0.985
8:39917902:T:A	W39R	0.983
8:39917902:T:C	W39R	0.983
8:39928001:G:T	R343M	0.983
8:39918833:G:C	A108P	0.982
8:39925314:A:C	S267R	0.982
8:39925316:C:A	S267R	0.982
8:39925316:C:G	S267R	0.982
8:39928001:G:C	R343T	0.981
8:39928002:G:C	R343S	0.980
8:39928002:G:T	R343S	0.980
8:39918910:C:A	N133K	0.978
8:39918910:C:G	N133K	0.978
8:39924741:T:C	F226L	0.977
8:39924743:T:A	F226L	0.977
8:39924743:T:G	F226L	0.977
8:39925302:A:C	S263R	0.977
8:39925304:T:A	S263R	0.977

dbSNP variants (sampled 300 via entrez): RS1000000684 (8:39923212 T>C), RS1000011915 (8:39926512 T>C), RS1000031494 (8:39923361 G>A), RS1000144856 (8:39920314 T>G), RS1000272871 (8:39928808 A>G), RS1000639729 (8:39924479 ACTTGTTACGT>A), RS1000659166 (8:39917777 T>C,G), RS1000765766 (8:39928725 T>C), RS1000873500 (8:39927429 G>A,C,T), RS1000899061 (8:39927544 A>C), RS1001000189 (8:39922072 C>T), RS1001340966 (8:39925566 A>C,G), RS1001350085 (8:39927810 T>A,C), RS1001675326 (8:39924532 A>G), RS1001938416 (8:39919503 T>C)

Disease associations

OMIM: gene MIM:147435 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4685 (SINGLE PROTEIN), CHEMBL4742272 (PROTEIN-PROTEIN INTERACTION), CHEMBL5169061 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 586,328 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL105	MITOMYCIN	4	233,273
CHEMBL1089	PHENELZINE	4	18,793
CHEMBL1201196	SERTACONAZOLE	4	9,003
CHEMBL1221	SULCONAZOLE	4	12,121
CHEMBL1262	OXICONAZOLE	4	48
CHEMBL157101	KETOCONAZOLE	4	75,361
CHEMBL1571863	ISOCONAZOLE	4	12,144
CHEMBL277535	BIFONAZOLE	4	12,513
CHEMBL295124	BERBERINE	4	26,682
CHEMBL590	MENADIONE	4	21,034
CHEMBL808	ECONAZOLE	4	24,813
CHEMBL91	MICONAZOLE	4	45,914
CHEMBL3545369	EPACADOSTAT	3	6,082
CHEMBL4297598	LINRODOSTAT	3	1,679
CHEMBL51085	EBSELEN	3	13,237
CHEMBL15192	LAPACHONE	2	589
CHEMBL33845	DICHLOROPHEN	2	29,496
CHEMBL356918	ENILCONAZOLE	2	34,679
CHEMBL3989951	NAVOXIMOD	2	3,496
CHEMBL571209	INDOXIMOD	2	5,371
CHEMBL4086143	PF-06840003	1
CHEMBL4778760	LY-3381916	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9657182	Toxicity	3	interferon alfa-2a;recombinant;peginterferon alfa-2b	Chronic hepatitis C virus infection

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs9657182	IDO1	3	1.50	1	interferon alfa-2a;recombinant;peginterferon alfa-2b

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — 1.13.11.- Dioxygenases

Most potent curated ligand interactions (11 total), top 11:

Ligand	Action	Affinity	Parameter
navoximod	Inhibition	8.24	pKi
epacadostat	Inhibition	7.17	pIC50
compound 8u [PMID: 31999451]	Inhibition	7.1	pKd
tryptanthrin 5i	Inhibition	6.99	pIC50
PF-06840003	Inhibition	6.82	pIC50
LW106	Inhibition	5.8	pIC50
amg-1	Inhibition	5.52	pIC50
tryptanthrin	Inhibition	5.32	pKi
necrostatin-1	Inhibition	4.94	pKi
1-methyl-L-tryptophan	Inhibition	4.37	pKi
beta-carboline	Inhibition	0.92	pKi

Binding affinities (BindingDB)

410 measured of 852 human assays (855 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
cis-(1R,2S)-2-[4-[cyclohexyl(2-methylpropyl)amino]-3-[(3-methyl-1,2-oxazol-5-yl)carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	0.5 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
3-[4-[bis(2-methylpropyl)amino]-3-[(2,4-difluorophenyl)carbamoylamino]phenyl]-4,4,4-trifluorobutanoic acid	IC50	0.7 nM	US-9624188: IDO inhibitors
3-[4-[cyclohexyl(2-methylpropyl)amino]-3-[(4-methylphenyl)carbamoylamino]phenyl]butanoic acid	IC50	1 nM	US-9624188: IDO inhibitors
methyl 2-[4-[bis(2-methylpropyl)amino]-3-nitrophenyl]cyclopropane-1-carboxylate	EC50	2 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
cis-(1R,2S)-2-[4-[bis(2-methylpropyl)amino]-3-[(3-cyclopropyl-1,2-oxazol-5-yl)carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	2 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
3-[4-[bis(2-methylpropyl)amino]-3-[(3-methyl-1,2-oxazol-5-yl)carbamoylamino]phenyl]butanoic acid	IC50	3 nM	US-9624188: IDO inhibitors
cis-(1S,2R)-2-[4-[bis(2-methylpropyl)amino]-3-[(3-methyl-1,2-oxazol-5-yl)carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	4 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
1-[3-bromo-2-heptan-4-yloxy-5-[2-(2H-tetrazol-5-yl)phenyl]phenyl]-3-(2-fluorophenyl)urea	IC50	4.49 nM	US-9765018: IDO inhibitors
(3R)-3-[4-[bis(2-methylpropyl)amino]-3-[[2-(4-cyanophenyl)acetyl]amino]phenyl]butanoic acid	IC50	5 nM	US-9624188: IDO inhibitors
CHEMBL3747340	IC50	5 nM
1-(5-Butyl-4-propoxy-2′-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-3-yl)-3-(p-tolyl)urea	IC50	5.92 nM	US-9765018: IDO inhibitors
cis-(1R,2S)-2-[4-[bis(2-methylpropyl)amino]-3-[(3-methyl-1,2-oxazol-5-yl)carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	6 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
1-(2-fluorophenyl)-3-[3-[(E)-pent-2-enyl]-2-propoxy-5-[2-(2H-tetrazol-5-yl)phenyl]phenyl]urea	IC50	6.49 nM	US-9765018: IDO inhibitors
cis-(1R,2S)-2-[4-[bis(2-methylpropyl)amino]-3-[[3-(trifluoromethyl)-1,2-oxazol-5-yl]carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	7 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
cis-(1S,2R)-2-[4-[bis(2-methylpropyl)amino]-3-[[3-(trifluoromethyl)-1,2-oxazol-5-yl]carbamoylamino]phenyl]cyclopropane-1-carboxylic acid	EC50	7 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
3-[4-[bis(2-methylpropyl)amino]-3-[[3-(trifluoromethyl)-1,2-oxazol-5-yl]carbamoylamino]phenyl]butanoic acid	IC50	7 nM	US-9624188: IDO inhibitors
cis-methyl (1S,2R)-2-[4-[bis(2-methylpropyl)amino]-3-nitrophenyl]cyclopropane-1-carboxylate	EC50	8 nM	US-9675571: Inhibitors of indoleamine 2,3-dioxygenase (IDO)
(E)-1-(4-Prop oxy-2′-(1H-tetrazol-5-yl)-5-(4,4,4-trifluorobut-2-en-1-yl)-[1,1′-biphenyl]-3-yl)-3-(p-tolyl)urea	IC50	10 nM	US-9765018: IDO inhibitors
(3R)-3-[4-[bis(2-methylpropyl)amino]-3-(pyrimidin-5-ylcarbamoylamino)phenyl]butanoic acid	IC50	11 nM	US-9624188: IDO inhibitors
(3S)-3-[4-[bis(2-methylpropyl)amino]-3-[(4-methylphenyl)carbamoylamino]phenyl]butanoic acid	IC50	17 nM	US-9624188: IDO inhibitors
(E)-1-(5-(4,4-Difluorobuta-1,3-dien-1-yl)-4-propoxy-2′-(1H-tetrazol-5-yl)-[1,1′-biphenyl]-3-yl)-3-(p-tolyl)urea	IC50	20 nM	US-9765018: IDO inhibitors
1-(4-Propoxy-2′-(1H-tetrazol-5-yl)-5-(4,4,4-trifluorobutyl)-[1,1′-biphenyl]-3-yl)-3-(p-tolyl)urea	IC50	20 nM	US-9765018: IDO inhibitors
3′-(3-Phenylpropyl)-4′-propoxy-5′-(3-p-tolylureido)biphenyl-2-carboxylic acid	IC50	20 nM	US-9765018: IDO inhibitors
1-(4-methylphenyl)-3-[3-pentyl-2-propoxy-5-[2-(2H-tetrazol-5-yl)phenyl]phenyl]urea	IC50	20 nM	US-9765018: IDO inhibitors
Methyl 3-chloro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carboxylate	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
N-(3-Chloro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-8-yl)acetamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Chloro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carboxamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1,3-Difluoro-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Fluoro-8-(methylsulfonyl)indolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
8-Fluoro-3-((4-methylpiperazin-1-yl)methyl)indolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Amino-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
tert-Butyl (8-nitro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazolin-3-yl)carbamate	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1,3-Dichloro-N-methyl-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carboxamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1,3-Dichloro-6,12-dioxoindolo[2,1-b]quinazoline-8-carboxamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1,3-Dichloro-N,N-dimethyl-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carboxamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Bromo-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carbonitrile	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
8-(Benzylthio)-3-fluoroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Fluoro-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-sulfonamide	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Fluoro-4-methyl-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
3-Fluoro-6-hydroxy-12-oxo-5,5a,6,12-tetrahydroindolo[2,1-b]quinazoline-8-carbonitrile	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1,3-Difluoro-6-hydroxy-8-nitro-5a,6-dihydroindolo[2,1-b]quinazolin-12(5H)-one	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-bromo-3-fluoro-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Chloro-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1-Chloro-8-nitroindolo[2,1-b]quinazolin-12(5H)-one	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
1-fluoro-4-methyl-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Fluoro-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Bromo-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Bromo-8-fluoroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
4-Bromo-2-fluoro-8-nitroindolo[2,1-b]quinazoline-6,12-dione	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF
Synthesis of 4-bromo-6,12-dioxo-6,12-dihydroindolo[2,1-b]quinazoline-8-carbonitrile	IC50	20 nM	US-20250171452: TRYPTANTHRIN DERIVATIVES AND USES THEREOF

ChEMBL bioactivities

4710 potent at pChembl≥5 of 5426 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.74	IC50	0.018	nM	CHEMBL432537
10.10	IC50	0.08	nM	CHEMBL5207194
10.05	IC50	0.09	nM	CHEMBL4645108
10.00	IC50	0.1	nM	CHEMBL4863767
9.96	Ki	0.11	nM	CHEMBL5192384
9.92	IC50	0.12	nM	PF-06840003
9.89	IC50	0.13	nM	CHEMBL4855797
9.82	Ki	0.15	nM	CHEMBL5192977
9.80	Kd	0.158	nM	CHEMBL5192977
9.64	IC50	0.23	nM	CHEMBL4161733
9.54	IC50	0.29	nM	CHEMBL4848630
9.54	IC50	0.29	nM	CHEMBL5192384
9.47	IC50	0.34	nM	CHEMBL4848098
9.35	IC50	0.45	nM	CHEMBL4872023
9.30	IC50	0.5	nM	CHEMBL3745883
9.30	IC50	0.5	nM	CHEMBL4161733
9.30	IC50	0.5	nM	LINRODOSTAT
9.30	EC50	0.5	nM	CHEMBL3745883
9.28	IC50	0.52	nM	CHEMBL4873747
9.23	IC50	0.59	nM	CHEMBL4879235
9.23	IC50	0.59	nM	CHEMBL4861457
9.22	IC50	0.6	nM	CHEMBL4642946
9.22	IC50	0.6	nM	CHEMBL4856710
9.20	IC50	0.63	nM	CHEMBL4869600
9.20	IC50	0.63	nM	CHEMBL5852167
9.19	IC50	0.64	nM	CHEMBL4867998
9.18	IC50	0.66	nM	CHEMBL5928626
9.16	IC50	0.6928	nM	CHEMBL4862659
9.16	IC50	0.69	nM	CHEMBL4858888
9.16	IC50	0.69	nM	CHEMBL5830508
9.15	IC50	0.7	nM	CHEMBL3746887
9.14	IC50	0.73	nM	CHEMBL4848366
9.11	IC50	0.78	nM	CHEMBL6047285
9.11	IC50	0.78	nM	CHEMBL6063420
9.10	IC50	0.8	nM	CHEMBL4764710
9.10	IC50	0.8	nM	CHEMBL5173861
9.09	IC50	0.82	nM	CHEMBL5744106
9.09	IC50	0.81	nM	CHEMBL5921667
9.08	IC50	0.84	nM	CHEMBL4855740
9.07	IC50	0.86	nM	CHEMBL4858599
9.07	IC50	0.85	nM	CHEMBL5997731
9.06	IC50	0.87	nM	CHEMBL5814507
9.04	IC50	0.92	nM	CHEMBL4849690
9.03	IC50	0.93	nM	CHEMBL5938257
9.02	IC50	0.9583	nM	CHEMBL4848644
9.01	IC50	0.98	nM	CHEMBL4849622
9.01	IC50	0.9819	nM	CHEMBL4865877
9.01	IC50	0.98	nM	CHEMBL5787202
9.01	IC50	0.97	nM	CHEMBL5772555
9.00	IC50	1	nM	CHEMBL4746602

PubChem BioAssay actives

2828 with measured affinity, of 6100 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
8-nitroindolo[2,1-b]quinazoline-6,12-dione	1053471: Inhibition of human IDO1 expressed in HEK293 cells assessed as kynurenine release after 5 hrs by spectrophotometry	ic50	<0.0001	uM
3-[4-[(3-chlorobenzoyl)amino]phenyl]-N-(4-fluorophenyl)oxetane-3-carboxamide	1903936: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as unbound concentration using kynurenine/tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for 18 hrs by LC/MS/MS analysis	ic50	0.0001	uM
N-(4-fluorophenyl)-3-[4-[4-(hydroxymethyl)-6-(trifluoromethyl)-3-pyridinyl]phenyl]oxetane-3-carboxamide	1903947: Displacement of [3H] labeled-N-(4-Fluorophenyl)-3-(4-(4-(2-hydroxypropan-2-yl)-6-(trifluoromethyl)pyridin-3-yl)phenyl)oxetane-3-carboxamide from human IDO1 assessed as inhibition constant by radioligand binding assay	ki	0.0001	uM
N-(4-fluorophenyl)-3-[4-[4-(2-hydroxypropan-2-yl)-6-(trifluoromethyl)-3-pyridinyl]phenyl]oxetane-3-carboxamide	1903947: Displacement of [3H] labeled-N-(4-Fluorophenyl)-3-(4-(4-(2-hydroxypropan-2-yl)-6-(trifluoromethyl)pyridin-3-yl)phenyl)oxetane-3-carboxamide from human IDO1 assessed as inhibition constant by radioligand binding assay	ki	0.0001	uM
3-[4-(6-cyclopropyl-4-methyl-3-pyridinyl)phenyl]-N-(4-fluorophenyl)oxetane-3-carboxamide	1903936: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as unbound concentration using kynurenine/tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for 18 hrs by LC/MS/MS analysis	ic50	0.0001	uM
(2R)-2-[1-(3-chlorobenzoyl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-yl]-N-(4-fluorophenyl)propanamide	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0001	uM
N-(4-fluorophenyl)-1-[1-[2-(trifluoromethyl)pyrimidin-4-yl]-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-yl]cyclobutane-1-carboxamide	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0001	uM
3-(5-fluoro-1H-indol-3-yl)pyrrolidine-2,5-dione	1916731: Inhibition of IDO1 (unknown origin)	ic50	0.0001	uM
N-(4-chlorophenyl)-1-(1-pyridin-2-yl-2,3-dihydropyrrolo[3,2-b]pyridin-5-yl)cyclobutane-1-carboxamide	1755112: Inhibition of human IDO1 assessed as unbound compound concentration by human whole blood assay	ic50	0.0003	uM
N-(4-fluorophenyl)-1-[1-(2-methylpyrimidin-4-yl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-yl]cyclobutane-1-carboxamide	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0003	uM
cyclopropyl 5-[1-[(4-fluorophenyl)carbamoyl]cyclobutyl]-2,3-dihydroindole-1-carboxylate	1755112: Inhibition of human IDO1 assessed as unbound compound concentration by human whole blood assay	ic50	0.0004	uM
(2R)-N-(4-chlorophenyl)-2-[4-(6-fluoroquinolin-4-yl)cyclohexyl]propanamide	1558485: Inhibition of IDO1 (unknown origin) by cell-based assay	ic50	0.0005	uM
1-(4-chlorophenyl)-N-[[(1R,5S)-3-(5,6-difluorobenzimidazol-1-yl)-6-bicyclo[3.1.0]hexanyl]methyl]-2,2,2-trifluoroethanamine	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0005	uM
1-[4-(2,3-dimethylphenyl)piperazin-1-yl]-2-[(2R,4R)-9-[4-(2-hydroxyethoxy)piperidine-1-carbonyl]-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]ethanone	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0005	uM
1-[(2R,4R)-7-[2-[4-(2,3-dimethylphenyl)piperazin-1-yl]-2-oxoethyl]-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-diene-9-carbonyl]piperidin-4-one	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0005	uM
1-[4-(2,3-dimethylphenyl)piperazin-1-yl]-2-[(2R,4R)-9-[5-(hydroxymethyl)-2-azabicyclo[3.1.1]heptane-2-carbonyl]-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]ethanone	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0005	uM
3-chloro-N-[3-[(2S)-1-(4-chloroanilino)-1-oxopropan-2-yl]-1-bicyclo[1.1.1]pentanyl]benzamide	1661736: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells using L-tryptophan as substrate incubated for 48 hrs by fluorescence assay	ic50	0.0006	uM
4-chloro-N-[1-[(1R,5S)-3-(6-fluoroquinolin-4-yl)-6-bicyclo[3.1.0]hexanyl]ethyl]benzamide	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0006	uM
N-[1-[3-[2-[4-(2-chloro-3-methylphenyl)piperazin-1-yl]-2-oxoethyl]-4a,5,6,7,8,8a-hexahydro-4H-indeno[2,1-c]pyrazole-1-carbonyl]piperidin-4-yl]acetamide	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0006	uM
1-[7-(4-fluoro-2,3-dimethylphenyl)-4,7-diazaspiro[2.5]octan-4-yl]-2-[(2R,4R)-9-[4-hydroxy-3-(hydroxymethyl)piperidine-1-carbonyl]-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]ethanone	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0006	uM
cyclopropyl 5-[1-[(4-chlorobenzoyl)amino]cyclobutyl]-2,3-dihydropyrrolo[3,2-b]pyridine-1-carboxylate	1755112: Inhibition of human IDO1 assessed as unbound compound concentration by human whole blood assay	ic50	0.0006	uM
1-[4-(2,3-dimethylphenyl)piperazin-1-yl]-2-[(2R,4R)-9-[(3R,4R)-3-fluoro-4-hydroxypiperidine-1-carbonyl]-7,8-diazatricyclo[4.3.0.02,4]nona-1(6),8-dien-7-yl]ethanone	1774651: Inhibition of IDO1 in IFN-gamma stimulated human HeLa cells incubated for 48 hrs by fluorescence microplate reader assay	ic50	0.0006	uM
cyclopropyl 6-[1-(6-chloro-1H-benzimidazol-2-yl)cyclobutyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0007	uM
cyclopropyl 6-[1-(4-chloroanilino)-1-oxopropan-2-yl]-2,3,4,4a,5,7,8,8a-octahydro-1,6-naphthyridine-1-carboxylate	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0007	uM
4-chloro-N-[1-[(1R,5S)-3-(5,6-difluorobenzimidazol-1-yl)-6-bicyclo[3.1.0]hexanyl]ethyl]benzamide	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0007	uM
3,3-difluoro-N-(4-fluorophenyl)-1-[4-[4-(hydroxymethyl)-6-(trifluoromethyl)-3-pyridinyl]phenyl]cyclobutane-1-carboxamide	1903936: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as unbound concentration using kynurenine/tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for 18 hrs by LC/MS/MS analysis	ic50	0.0008	uM
1-[1-(3-chlorobenzoyl)-2,3-dihydropyrrolo[3,2-b]pyridin-5-yl]-N-(4-fluorophenyl)cyclobutane-1-carboxamide	1755112: Inhibition of human IDO1 assessed as unbound compound concentration by human whole blood assay	ic50	0.0008	uM
cyclobutyl 6-[(1R)-1-[(4-fluorobenzoyl)amino]ethyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1694669: Inhibition of IDO1 in IFN-gamma-stimulated human HeLa cells assessed as reduction in kynurenine production using L-Tryptophan as substrate incubated for 48 hrs by fluorescence based assay	ic50	0.0008	uM
1-[1-(cyclopropanecarbonyl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-yl]-N-(4-fluorophenyl)cyclobutane-1-carboxamide	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0009	uM
4-[(1S,5R)-6-[1-(6-chloro-1H-benzimidazol-2-yl)propyl]-3-bicyclo[3.1.0]hexanyl]-6-fluoroquinoline	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0009	uM
N’-(3-chlorophenyl)-3-cyclohexyl-N-hydroxypropanimidamide	1882075: Inhibition of IDO1 (unknown origin)	ic50	0.0010	uM
3,7-dibenzyltriazolo[4,5-f]benzotriazole-4,8-dione	1728747: Inhibition of human IDO1	ic50	0.0010	uM
4-chloro-N-[1-[(1R,5S)-3-(6-fluoroquinolin-4-yl)oxy-6-bicyclo[3.1.0]hexanyl]propyl]benzamide	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0010	uM
cyclopropyl 6-[(1S)-1-(6-chloro-1H-benzimidazol-2-yl)ethyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0010	uM
(2-chlorophenyl)-[6-[1-[6-(trifluoromethyl)-1H-imidazo[4,5-b]pyridin-2-yl]cyclobutyl]-3,4-dihydro-2H-1,5-naphthyridin-1-yl]methanone	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0010	uM
1-[1-(3-chlorobenzoyl)-3,4,4a,5,6,7,8,8a-octahydro-2H-quinolin-6-yl]-N-(4-fluorophenyl)cyclobutane-1-carboxamide	1752243: Inhibition of IDO1 in human whole blood assessed as unbound concentration	ic50	0.0010	uM
4-fluoro-N-[(1S,2S)-2-methyl-1-[5-(2-methylpyrimidin-4-yl)-7,8-dihydro-6H-1,5-naphthyridin-2-yl]cyclopropyl]benzamide	1769198: Inhibition of IDO1 in human HeLa cells	ic50	0.0011	uM
cyclopropyl 6-[1-(6-chloro-1H-benzimidazol-2-yl)ethyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0011	uM
N-(4-fluorophenyl)-1-[4-[4-(hydroxymethyl)-6-(trifluoromethyl)-3-pyridinyl]phenyl]cyclobutane-1-carboxamide	1903936: Inhibition of IDO1 in IFNgamma/LPS stimulated human whole blood assessed as unbound concentration using kynurenine/tryptophan as substrate preincubated with compound for 15 mins followed by incubation with IFNgamma/LPS for 18 hrs by LC/MS/MS analysis	ic50	0.0012	uM
4-fluoro-N-[1-[5-[2-(trifluoromethyl)pyrimidin-4-yl]-7,8-dihydro-6H-1,5-naphthyridin-2-yl]cyclopropyl]benzamide	1769198: Inhibition of IDO1 in human HeLa cells	ic50	0.0012	uM
4-fluoro-N-[1-[5-(2-methylpyrimidin-4-yl)-7,8-dihydro-6H-1,5-naphthyridin-2-yl]cyclopropyl]benzamide	1769198: Inhibition of IDO1 in human HeLa cells	ic50	0.0012	uM
cyclopropyl 6-[1-[6-(trifluoromethyl)-1H-imidazo[4,5-b]pyridin-2-yl]cyclobutyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0013	uM
cyclopropyl 6-[1-(6-chloro-1H-imidazo[4,5-b]pyridin-2-yl)cyclobutyl]-3,4-dihydro-2H-1,5-naphthyridine-1-carboxylate	1769406: Inhibition of IDO1 in IFN-gamma induced human HeLa cells measured after 48 hrs by fluorescence assay	ic50	0.0014	uM
N-[(1R)-1-[5-(3-chlorobenzoyl)-7,8-dihydro-6H-1,5-naphthyridin-2-yl]ethyl]-4-fluorobenzamide	1694669: Inhibition of IDO1 in IFN-gamma-stimulated human HeLa cells assessed as reduction in kynurenine production using L-Tryptophan as substrate incubated for 48 hrs by fluorescence based assay	ic50	0.0014	uM
4-chloro-N-[1-[(1R,5S)-3-(7-fluoroquinolin-4-yl)oxy-6-bicyclo[3.1.0]hexanyl]propyl]benzamide	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0014	uM
1-(4-methylphenyl)-3-[7-[2-(3-oxo-1,2,4-oxadiazol-5-yl)phenyl]-5-phenyl-2,3,4,5-tetrahydro-1-benzoxepin-9-yl]urea	1955435: Inhibition of IDO1 (unknown origin) expressed in human HeLa cells	ic50	0.0015	uM
(NZ)-N-[(4-amino-1,2,5-oxadiazol-3-yl)-(1,3-dihydroisoindol-2-yl)methylidene]hydroxylamine	1882075: Inhibition of IDO1 (unknown origin)	ic50	0.0016	uM
4-chloro-N-[1-[(1R,5S)-3-quinolin-4-yloxy-6-bicyclo[3.1.0]hexanyl]propyl]benzamide	1783469: Inhibition of IDO1 in human HeLa cells using tryptophan as substrate incubated for 24 hrs by RFMS assay	ic50	0.0016	uM
4-chloro-N-[(1R)-1-[5-(3-chlorobenzoyl)-7,8-dihydro-6H-1,5-naphthyridin-2-yl]ethyl]benzamide	1694669: Inhibition of IDO1 in IFN-gamma-stimulated human HeLa cells assessed as reduction in kynurenine production using L-Tryptophan as substrate incubated for 48 hrs by fluorescence based assay	ic50	0.0016	uM
N-(4-chlorophenyl)-1-(1-pyridin-2-yl-2,3-dihydroindol-5-yl)cyclobutane-1-carboxamide	1755110: Inhibition of human IDO1 in human Hela cells	ic50	0.0016	uM

CTD chemical–gene interactions

72 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Cisplatin	affects expression, decreases response to substance, increases expression	3
Lipopolysaccharides	decreases reaction, increases expression, affects cotreatment	3
epacadostat	decreases reaction, increases expression, decreases activity, decreases expression	2
6-formylindolo(3,2-b)carbazole	increases expression	2
entinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, decreases expression, affects activity	2
Benzo(a)pyrene	increases expression, increases methylation	2
Cannabidiol	decreases reaction, increases activity, increases reaction, increases abundance, increases expression	2
Nickel	increases expression	2
Quercetin	affects binding, increases expression	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression, decreases reaction	1
TL8-506	increases expression, affects cotreatment	1
2,4,6-tribromophenol	decreases expression	1
testosterone enanthate	affects expression	1
salinomycin	affects binding, decreases activity, decreases reaction, increases expression	1
decabromobiphenyl ether	decreases expression	1
trichostatin A	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
2-oxindole	increases expression	1
nickel sulfate	increases expression	1
CMF regimen	affects response to substance	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression, decreases reaction	1
indeno(1,2,3-cd)pyrene	increases expression	1
gadodiamide	increases expression	1
3’-methoxy-4’-nitroflavone	increases expression, decreases reaction	1
iodopravadoline	decreases reaction, increases activity, increases reaction	1
AM 281	increases activity, increases reaction, decreases reaction	1

ChEMBL screening assays

927 unique, capped per target: 924 binding, 3 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1005552	Binding	Inhibition of human recombinant indoleamine 2,3-dioxygenase in presence of L-tryptophan substrate	Structure based development of phenylimidazole-derived inhibitors of indoleamine 2,3-dioxygenase. — J Med Chem
CHEMBL3993124	ADMET	Inhibition of recombinant human IDO expressed in Escherichia coli assessed as reduction in kynurenine production at 200 uM using L-tryptophan as substrate after 3 hrs by methylene blue dye based assay	Discovery of a Highly Potent, Selective, and Metabolically Stable Inhibitor of Receptor-Interacting Protein 1 (RIP1) for the Treatment of Systemic Inflammatory Response Syndrome. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1FN	Abcam A-549 IDO1 KO 1	Cancer cell line	Male
CVCL_B2N7	Abcam A-549 IDO1 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.