Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DEGH1QU)

• DME Name: Tryptophan oxygenase (TRPO)
• Synonyms: Tryptamin 2,3-dioxygenase; Tryptophan 2,3-dioxygenase; Tryptophan pyrrolase; Tryptophanase; TDO; TDO2; TO; TRPO
• Gene Name: TDO2
• UniProt ID: T23O_HUMAN
• INTEDE ID: DME0172
• Gene ID: 6999
• EC Number:
  EC: 1.13.11.11
  Oxidoreductase
  Oxygen single donor oxidoreductase
  Oxygen single donor oxidoreductase
  EC: 1.13.11.11
• Lineage:
  Species: Homo sapiens
  Kingdom: Metazoa
  Phylum: Chordata
  Class: Mammalia
  Order: Primates
  Family: Hominidae
  Genus: Homo
  Species: Homo sapiens
• Sequence:
  MSGCPFLGNNFGYTFKKLPVEGSEEDKSQTGVNRASKGGLIYGNYLHLEKVLNAQELQSE
  TKGNKIHDEHLFIITHQAYELWFKQILWELDSVREIFQNGHVRDERNMLKVVSRMHRVSV
  ILKLLVQQFSILETMTALDFNDFREYLSPASGFQSLQFRLLENKIGVLQNMRVPYNRRHY
  RDNFKGEENELLLKSEQEKTLLELVEAWLERTPGLEPHGFNFWGKLEKNITRGLEEEFIR
  IQAKEESEEKEEQVAEFQKQKEVLLSLFDEKRHEHLLSKGERRLSYRALQGALMIYFYRE
  EPRFQVPFQLLTSLMDIDSLMTKWRYNHVCMVHRMLGSKAGTGGSSGYHYLRSTVSDRYK
  VFVDLFNLSTYLIPRHWIPKMNPTIHKFLYTAEYCDSSYFSSDESD
• Function: This enzyme catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L- tryptophan to N-formyl-L-kynurenine. It catalyzes the oxidative cleavage of the indole moiety.
• KEGG Pathway:
  Metabolic pathways (hsa01100)
  Tryptophan metabolism (hsa00380)
• Reactome Pathway: Tryptophan catabolism (R-HSA-71240)

Molecular Interaction Atlas (MIA) of This DME

1 Approved Drug(s) Metabolized by This DME

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
L-Tryptophan	DMIBH7M	Depression	6A70-6A7Z	Approved	[8]

Molecular Expression Atlas (MEA) of This DME

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Acute myelocytic leukaemia	2B33.1	Bone marrow	2.25E-01	9.04E-03	3.66E-02
Alopecia	ED70	Skin from scalp	4.56E-02	5.50E-02	2.44E-01
Alzheimer's disease	8A20	Entorhinal cortex	1.26E-02	-9.71E-02	-2.35E-01
Ankylosing spondylitis	FA92.0	Pheripheral blood	2.41E-01	-1.28E-01	-8.77E-01
Aortic stenosis	BB70	Calcified aortic valve	4.38E-04	1.37E+00	1.81E+00
Apnea	7A40	Hyperplastic tonsil	4.85E-01	5.21E-02	2.37E-01
Arthropathy	FA00-FA5Z	Peripheral blood	3.70E-01	6.12E-02	6.43E-01
Asthma	CA23	Nasal and bronchial airway	5.45E-05	3.49E-01	6.98E-01
Atopic dermatitis	EA80	Skin	1.31E-04	1.38E-01	7.16E-01
Autism	6A02	Whole blood	4.32E-01	-3.08E-02	-2.33E-01
Autoimmune uveitis	9A96	Peripheral monocyte	1.05E-01	-9.67E-02	-7.56E-01
Autosomal dominant monocytopenia	4B04	Whole blood	8.47E-01	-5.02E-02	-5.15E-01
Bacterial infection of gingival	1C1H	Gingival tissue	2.27E-21	7.60E-01	1.97E+00
Batten disease	5C56.1	Whole blood	3.18E-01	-1.90E-02	-2.91E-01
Behcet's disease	4A62	Peripheral blood	1.44E-03	1.44E-01	1.15E+00
Bipolar disorder	6A60-6A6Z	Prefrontal cortex	7.35E-01	8.38E-03	2.81E-02
Bladder cancer	2C94	Bladder tissue	9.56E-15	1.63E+00	9.08E+00
Breast cancer	2C60-2C6Z	Breast tissue	2.27E-198	9.52E-01	3.66E+00
Cardioembolic stroke	8B11.20	Whole blood	7.70E-03	6.76E-02	4.79E-01
Cervical cancer	2C77	Cervical tissue	3.45E-03	2.49E-01	8.98E-01
Childhood onset rheumatic disease	FA20.Z	Peripheral blood	7.02E-01	3.92E-02	2.35E-01
Chronic hepatitis C	1E51.1	Whole blood	5.29E-02	3.30E-02	2.60E-01
Chronic obstructive pulmonary disease	CA22	Lung tissue	1.24E-01	3.71E-01	6.46E-01
Chronic obstructive pulmonary disease	CA22	Small airway epithelium	1.41E-01	1.92E-02	1.51E-01
Chronic rhinosinusitis	CA0A	Sinus mucosa tissue	4.37E-02	1.89E-01	1.08E+00
Colon cancer	2B90	Colon tissue	1.09E-40	6.72E-01	1.46E+00
Coronary artery disease	BA80-BA8Z	Peripheral blood	3.12E-01	-1.43E-01	-8.14E-01
Diffuse large B-cell lymphoma	2A81	Tonsil tissue	4.17E-01	1.34E-02	9.19E-02
Endometriosis	GA10	Endometrium tissue	4.04E-01	-1.40E-01	-1.41E-01
Familial hypercholesterolemia	5C80.00	Peripheral blood	5.51E-01	-8.67E-02	-6.58E-01
Familial hypercholesterolemia	5C80.00	Whole blood	5.67E-04	-2.76E-01	-1.44E+00
Gastric cancer	2B72	Gastric tissue	2.47E-03	9.57E-01	7.09E+00
Glioblastopma	2A00.00	Nervous tissue	5.24E-01	-8.98E-02	-2.04E-01
Glioma	2A00.0Y-2A00.0Z	Brain stem tissue	2.79E-01	-8.23E-02	-2.05E+00
Glioma	2A00.0Y-2A00.0Z	White matter tissue	6.02E-03	4.17E-01	1.26E+00
Head and neck cancer	2D42	Head and neck tissue	1.02E-52	1.46E+00	5.78E+00
HIV-associated neurocognitive impairment	8A2Y-8A2Z	White matter tissue	5.54E-02	-2.04E-01	-6.06E-01
Huntington's disease	8A01.10	Whole blood	2.55E-01	-4.13E-02	-5.68E-01
Idiopathic pulmonary fibrosis	CB03.4	Lung tissue	2.70E-02	1.39E+00	1.77E+00
Immunodeficiency	4A00-4A20	Peripheral blood	6.21E-01	-1.37E-02	-1.55E-01
Influenza	1E30	Whole blood	5.11E-02	2.54E-01	2.01E+00
Interstitial cystitis	GC00.3	Bladder tissue	7.27E-06	2.02E+00	2.23E+01
Intracranial aneurysm	8B01.0	Intracranial artery	1.30E-02	6.90E-01	4.17E+00
Irritable bowel syndrome	DD91.0	Rectal colon tissue	3.81E-01	3.08E-02	5.09E-02
Ischemic stroke	8B11	Peripheral blood	1.41E-02	8.06E-02	7.70E-01
Juvenile idiopathic arthritis	FA24	Peripheral blood	6.51E-01	1.79E-02	9.07E-02
Lateral sclerosis	8B60.4	Skin	1.04E-01	7.85E-02	6.80E-01
Lateral sclerosis	8B60.4	Cervical spinal cord	1.01E-01	2.17E-01	1.51E+00
Liver cancer	2C12.0	Liver tissue	1.90E-24	-2.14E+00	-2.62E+00
Liver failure	DB99.7-DB99.8	Liver tissue	1.60E-05	-1.77E+00	-2.79E+00
Lung cancer	2C25	Lung tissue	6.45E-13	6.62E-01	9.00E-01
Lupus erythematosus	4A40	Whole blood	9.54E-01	-2.80E-02	-1.13E-01
Major depressive disorder	6A70-6A7Z	Hippocampus	9.33E-01	-6.25E-02	-2.12E-01
Major depressive disorder	6A70-6A7Z	Whole blood	9.47E-01	-1.24E-02	-6.44E-02
Melanoma	2C30	Skin	7.65E-07	1.03E+00	1.55E+00
Multiple myeloma	2A83.1	Peripheral blood	2.87E-02	1.41E-01	1.57E+00
Multiple myeloma	2A83.1	Bone marrow	9.81E-05	1.67E-01	1.33E+00
Multiple sclerosis	8A40	Plasmacytoid dendritic cells	6.92E-01	-5.73E-02	-2.52E-01
Myelodysplastic syndrome	2A36-2A3Z	Bone marrow	4.25E-04	9.17E-02	6.69E-01
Myelofibrosis	2A20.2	Whole blood	4.12E-01	-4.86E-02	-3.64E-01
Myocardial infarction	BA41-BA50	Peripheral blood	8.12E-02	1.41E-01	5.29E-01
Myopathy	8C70.6	Muscle tissue	1.51E-06	5.75E-01	3.77E+00
Neonatal sepsis	KA60	Whole blood	6.31E-01	4.03E-02	2.51E-01
Neuroectodermal tumour	2A00.11	Brain stem tissue	1.56E-02	-4.65E-01	-1.90E+00
Non-alcoholic fatty liver disease	DB92	Liver tissue	2.97E-02	4.79E-01	5.97E-01
Obesity related type 2 diabetes	5A11	Omental adipose tissue	2.51E-01	3.48E-02	4.03E-01
Olive pollen allergy	CA08.00	Peripheral blood	3.08E-01	4.50E-01	6.62E-01
Oral cancer	2B6E	Oral tissue	2.03E-15	1.26E+00	2.86E+00
Osteoarthritis	FA00-FA0Z	Synovial tissue	2.10E-01	3.25E-01	3.90E-01
Osteoporosis	FB83.1	Bone marrow	5.81E-01	-9.45E-02	-7.98E-01
Ovarian cancer	2C73	Ovarian tissue	3.70E-10	1.06E+00	5.74E+00
Pancreatic cancer	2C10	Pancreas	3.83E-04	8.97E-01	1.24E+00
Parkinson's disease	8A00.0	Substantia nigra tissue	2.71E-01	-1.37E-01	-4.68E-01
Pediatric respiratory syncytial virus infection	CA40.11	Peripheral blood	4.78E-01	1.90E-02	2.44E-01
Pituitary cancer	2D12	Pituitary tissue	3.59E-04	-1.52E+00	-2.18E+00
Pituitary gonadotrope tumour	2D12	Pituitary tissue	3.69E-04	-1.63E+00	-2.21E+00
Polycystic ovary syndrome	5A80.1	Vastus lateralis muscle	3.33E-01	-1.40E-01	-5.51E-01
Polycythemia vera	2A20.4	Whole blood	6.41E-06	1.12E-01	8.29E-01
Pompe disease	5C51.3	Biceps muscle	2.66E-01	-9.41E-02	-4.66E-01
Preterm birth	KA21.4Z	Myometrium	1.60E-01	-6.71E-02	-4.68E-01
Prostate cancer	2C82	Prostate	5.15E-02	-1.38E-01	-3.21E-01
Psoriasis	EA90	Skin	2.86E-27	4.53E-01	2.13E+00
Rectal cancer	2B92	Rectal colon tissue	1.23E-05	7.81E-01	3.18E+00
Renal cancer	2C90-2C91	Kidney	7.56E-03	2.06E-01	7.47E-01
Retinoblastoma	2D02.2	Uvea	1.83E-01	3.79E-02	5.37E-01
Rheumatoid arthritis	FA20	Synovial tissue	7.46E-01	1.94E-01	2.06E-01
Rhinovirus infection	CA42.1	Nasal epithelium tissue	5.47E-01	2.13E-02	1.39E-01
Schizophrenia	6A20	Prefrontal cortex	9.40E-02	-7.45E-02	-1.61E-01
Schizophrenia	6A20	Superior temporal cortex	5.82E-01	1.18E-02	7.43E-02
Scleroderma	4A42.Z	Whole blood	2.50E-01	1.40E-02	1.31E-01
Seizure	8A60-8A6Z	Whole blood	2.92E-01	-1.58E-01	-9.54E-01
Sensitive skin	EK0Z	Skin	9.30E-01	-2.90E-02	-3.63E-01
Sepsis with septic shock	1G41	Whole blood	1.31E-09	1.31E-01	7.99E-01
Shwachman-Diamond syndrome	3A70.0	Bone marrow	6.35E-02	2.61E-01	8.81E-01
Sickle cell disease	3A51.0-3A51.3	Peripheral blood	2.16E-01	8.16E-02	9.08E-01
Simpson golabi behmel syndrome	LD2C	Adipose tissue	5.78E-01	-2.66E-01	-5.03E-01
Sjogren's syndrome	4A43.2	Salivary gland tissue	3.95E-01	5.76E-02	7.79E-01
Skin cancer	2C30-2C3Z	Skin	6.71E-92	1.40E+00	4.27E+00
Thrombocythemia	3B63	Whole blood	5.15E-03	1.03E-01	8.23E-01
Thrombocytopenia	3B64	Whole blood	2.82E-01	-5.04E-02	-5.23E-01
Thyroid cancer	2D10	Thyroid	4.23E-24	1.14E+00	1.84E+00
Tibial muscular dystrophy	8C75	Muscle tissue	1.44E-06	1.39E+00	3.51E+00
Tuberous sclerosis complex	LD2D.2	Perituberal tissue	2.65E-01	-2.62E-01	-1.20E+00
Type 2 diabetes	5A11	Liver tissue	1.54E-01	6.37E-02	2.62E-01
Ureter cancer	2C92	Urothelium	3.54E-01	-6.75E-02	-3.51E-01
Uterine cancer	2C78	Endometrium tissue	4.47E-10	3.45E-01	7.68E-01
Vitiligo	ED63.0	Skin	9.28E-01	-1.52E-02	-3.94E-02

The Drug Therapeutic Target (DTT) Role of This DME

• DME DTT Name: Tryptophan 2,3-dioxygenase (TDO) DTT Info
• DME DTT Type: Clinical trial

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DN1406131	DMQFX8R	Solid tumour/cancer	2A00-2F9Z	Phase 1	[1]
HTI-1090	DMI4TEC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[2]

11 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	[3]
2,3-diamino-benzo[b]thiophene derivative 2	DMDYXKT	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 3	DMR7QKL	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 4	DMEDFNC	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 5	DM05WXD	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 6	DMINE6V	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 7	DMQVMNJ	N. A.	N. A.	Patented	[3]
2,3-diamino-benzo[b]thiophene derivative 8	DM5O8K0	N. A.	N. A.	Patented	[3]
Indazole derivative 3	DMVUWLK	N. A.	N. A.	Patented	[4]
PMID27172114-Compound-30	DMBWLSA	N. A.	N. A.	Patented	[3]
PMID29473428-Compound-76	DM8PZ46	N. A.	N. A.	Patented	[4]

5 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
4-(4-fluoropyrazol-1-yl)-1,2-oxazol-5-amine	DM57GL1	Solid tumour/cancer	2A00-2F9Z	Preclinical	[5]
680C91	DMCDTIG	Solid tumour/cancer	2A00-2F9Z	Preclinical	[6]
EPL-1410	DM5K17C	Solid tumour/cancer	2A00-2F9Z	Preclinical	[5]
LM10	DMXYDMP	Solid tumour/cancer	2A00-2F9Z	Preclinical	[7]
RG70099	DM7JH0K	Solid tumour/cancer	2A00-2F9Z	Preclinical	[5]

References

• [1] ClinicalTrials.gov (NCT03641794) Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers. U.S. National Institutes of Health.
• [2] 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.
• [3] Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
• [4] A patent review of IDO1 inhibitors for cancer.Expert Opin Ther Pat. 2018 Apr;28(4):317-330.
• [5] Tryptophan metabolism as a common therapeutic target in cancer, neurodegeneration and beyond. Nat Rev Drug Discov. 2019 May;18(5):379-401.
• [6] Effects of IDO1 and TDO2 inhibition on cognitive deficits and anxiety following LPS-induced neuroinflammation. Acta Neuropsychiatr. 2020 Feb;32(1):43-53.
• [7] The autoimmune response elicited by mouse hepatitis virus (MHV-A59) infection is modulated by liver tryptophan-2,3-dioxygenase (TDO). Immunol Lett. 2020 Jan;217:25-30.
• [8] Reaction pathway of tryptophanase-catalyzed L-tryptophan synthesis from D-serine. J Chromatogr B Analyt Technol Biomed Life Sci. 2011 Nov 1;879(29):3289-95.