Top ▲

tryptophan 2,3-dioxygenase

Click here for help

Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2887

Nomenclature: tryptophan 2,3-dioxygenase

Abbreviated Name: TDO2

Family: 1.13.11.- Dioxygenases

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 406 4q32.1 TDO2 tryptophan 2,3-dioxygenase
Mouse - 406 3 E3 Tdo2 tryptophan 2,3-dioxygenase
Rat - 406 2q34 Tdo2 tryptophan 2,3-dioxygenase
Previous and Unofficial Names Click here for help
tryptophan peroxidase | tryptophan pyrrolase | tryptophanase | indolamine 2,3-dioxygenase | tryptamine 2,3-dioxygenase | TDO | TPH2 | tryptophan 2
Database Links Click here for help
Alphafold
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction Click here for help
EC Number: 1.13.11.11
Description Reaction Reference
Together with IDO1, catalyzes the first and rate-limiting step in the kynurenine pathway (major pathway of tryptophan metabolism). L-tryptophan + O2 <=> N-formyl-L-kynurenine

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
LM10 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 5.3 pKi 1,3
pKi 5.3 (Ki 5.6x10-6 M) [1,3]
LM10 Small molecule or natural product Primary target of this compound Immunopharmacology Ligand Hs Inhibition 6.2 pIC50 3
pIC50 6.2 (IC50 6.2x10-7 M) [3]
Description: Concentration inhibiting TDO activity by 50% in a cellular assay, at 80μM L-tryptophan.
navoximod Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibition >6.0 pIC50 2
pIC50 >6.0 (IC50 <1x10-6 M) [2]
LM10 Small molecule or natural product Immunopharmacology Ligand Mm Inhibition 5.7 pIC50 3
pIC50 5.7 (IC50 1.96x10-6 M) [3]
Description: Concentration inhibiting TDO activity by 50% in a cellular assay, at 80μM L-tryptophan.
View species-specific inhibitor tables
Inhibitor Comments
LM10 is >640-fold selective for TDO2 over IDO1 [3].
Immunopharmacology Comments
Depletion of tryptophan and metabolites promote Treg cell differentiation, suppression of immune response and decreased DC function. TDO2 inhibition reverses this [3].

References

Show »

1. Dolusić E, Larrieu P, Moineaux L, Stroobant V, Pilotte L, Colau D, Pochet L, Van den Eynde B, Masereel B, Wouters J et al.. (2011) Tryptophan 2,3-dioxygenase (TDO) inhibitors. 3-(2-(pyridyl)ethenyl)indoles as potential anticancer immunomodulators. J Med Chem, 54 (15): 5320-34. [PMID:21726069]

2. Dounay AB, Tuttle JB, Verhoest PR. (2015) Challenges and Opportunities in the Discovery of New Therapeutics Targeting the Kynurenine Pathway. J Med Chem, 58 (22): 8762-82. [PMID:26207924]

3. Pilotte L, Larrieu P, Stroobant V, Colau D, Dolusic E, Frédérick R, De Plaen E, Uyttenhove C, Wouters J, Masereel B et al.. (2012) Reversal of tumoral immune resistance by inhibition of tryptophan 2,3-dioxygenase. Proc Natl Acad Sci USA, 109 (7): 2497-502. [PMID:22308364]

How to cite this page

1.13.11.- Dioxygenases: tryptophan 2,3-dioxygenase. Last modified on 03/07/2019. Accessed on 20/10/2021. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2887.