Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Tryptophan 2,3-dioxygenase (TDO)
• Synonyms: Tryptophanase; Tryptophan pyrrolase; Tryptophan oxygenase; Tryptamin 2,3-dioxygenase; TRPO; TO
• Gene Name: TDO2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Oxygenase
• UniProt ID: T23O_HUMAN
• TTD ID: T44818
• EC Number: EC 1.13.11.11
• Sequence:
  MSGCPFLGNNFGYTFKKLPVEGSEEDKSQTGVNRASKGGLIYGNYLHLEKVLNAQELQSE
  TKGNKIHDEHLFIITHQAYELWFKQILWELDSVREIFQNGHVRDERNMLKVVSRMHRVSV
  ILKLLVQQFSILETMTALDFNDFREYLSPASGFQSLQFRLLENKIGVLQNMRVPYNRRHY
  RDNFKGEENELLLKSEQEKTLLELVEAWLERTPGLEPHGFNFWGKLEKNITRGLEEEFIR
  IQAKEESEEKEEQVAEFQKQKEVLLSLFDEKRHEHLLSKGERRLSYRALQGALMIYFYRE
  EPRFQVPFQLLTSLMDIDSLMTKWRYNHVCMVHRMLGSKAGTGGSSGYHYLRSTVSDRYK
  VFVDLFNLSTYLIPRHWIPKMNPTIHKFLYTAEYCDSSYFSSDESD
• Function: Catalyzes the oxidative cleavage of the indole moiety. Heme-dependent dioxygenase that catalyzes the oxidative cleavage of the L-tryptophan (L-Trp) pyrrole ring and converts L-tryptophan to N-formyl-L-kynurenine.
• KEGG Pathway:
  Tryptophan metabolism (hsa00380)
  Metabolic pathways (hsa01100)
• Reactome Pathway: Tryptophan catabolism (R-HSA-71240)
• BioCyc Pathway: MetaCyc:HS07771-MON

Molecular Interaction Atlas (MIA) of This DTT

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	[2]
HTI-1090	DMI4TEC	Solid tumour/cancer	2A00-2F9Z	Phase 1	[3]

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	[4]
2,3-diamino-benzo[b]thiophene derivative 2	DMDYXKT	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 3	DMR7QKL	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 4	DMEDFNC	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 5	DM05WXD	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 6	DMINE6V	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 7	DMQVMNJ	N. A.	N. A.	Patented	[4]
2,3-diamino-benzo[b]thiophene derivative 8	DM5O8K0	N. A.	N. A.	Patented	[4]
Indazole derivative 3	DMVUWLK	N. A.	N. A.	Patented	[1]
PMID27172114-Compound-30	DMBWLSA	N. A.	N. A.	Patented	[4]
PMID29473428-Compound-76	DM8PZ46	N. A.	N. A.	Patented	[1]

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]

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

• DTT DME Name: Tryptophan oxygenase (TRPO) DME Info
• Gene Name: TDO2

1 Approved Drug(s) Metabolized by This DTT

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

References

• [1] A patent review of IDO1 inhibitors for cancer.Expert Opin Ther Pat. 2018 Apr;28(4):317-330.
• [2] ClinicalTrials.gov (NCT03641794) Indoleamine 2,3-Dioxygenase (IDO) Inhibitor in Healthy Volunteers. U.S. National Institutes of Health.
• [3] 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.
• [4] Inhibitors of the kynurenine pathway as neurotherapeutics: a patent review (2012-2015).Expert Opin Ther Pat. 2016 Jul;26(7):815-32.
• [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.