tryptophan 2,3-dioxygenase

Target id: 2887

Nomenclature: tryptophan 2,3-dioxygenase

Abbreviated Name: TDO2

Family: 1.13.11.- Dioxygenases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     tryptophan 2,3-dioxygenase has curated GtoImmuPdb data

Gene and Protein Information
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 2q33 Tdo2 tryptophan 2,3-dioxygenase
Previous and Unofficial Names
tryptophan peroxidase | tryptophan pyrrolase | tryptophanase | indolamine 2,3-dioxygenase | tryptamine 2,3-dioxygenase | TDO | TPH2 | tryptophan 2
Database Links
BRENDA
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
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

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
LM10 Hs Inhibition 5.3 pKi 1-2
pKi 5.3 (Ki 5.6x10-6 M) [1-2]
LM10 Hs Inhibition 6.2 pIC50 2
pIC50 6.2 (IC50 6.2x10-7 M) [2]
Description: Concentration inhibiting TDO activity by 50% in a cellular assay, at 80μM L-tryptophan.
LM10 Mm Inhibition 5.7 pIC50 2
pIC50 5.7 (IC50 1.96x10-6 M) [2]
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 [2].
Immunopharmacology Comments
Depletion of tryptophan and metabolites promote Treg cell differentiation, suppression of immune response and decreased DC function. TDO2 inhibition reverses this [2].

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. 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. U.S.A., 109 (7): 2497-502. [PMID:22308364]

How to cite this page

1.13.11.- Dioxygenases: tryptophan 2,3-dioxygenase. Last modified on 09/02/2016. Accessed on 18/06/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2887.