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tryptophan 2,3-dioxygenase

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Target id: 2887

Nomenclature: tryptophan 2,3-dioxygenase

Abbreviated Name: TDO2

Family: 1.13.11.- Dioxygenases

Contents:

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 P48775 (Hs), P48776 (Mm), P21643 (Rn)
BRENDA 1.13.11.11
ChEMBL Target CHEMBL2140 (Hs), CHEMBL1075307 (Mm), CHEMBL2686 (Rn)
Ensembl Gene ENSG00000151790 (Hs), ENSMUSG00000028011 (Mm), ENSRNOG00000011612 (Rn)
Entrez Gene 6999 (Hs), 56720 (Mm), 64206 (Rn)
Human Protein Atlas ENSG00000151790 (Hs)
KEGG Enzyme 1.13.11.11
KEGG Gene hsa:6999 (Hs), mmu:56720 (Mm), rno:64206 (Rn)
OMIM 191070 (Hs)
Pharos P48775 (Hs)
RefSeq Nucleotide NM_005651 (Hs), NM_019911 (Hs), NM_022403 (Rn)
RefSeq Protein NP_005642 (Hs), NP_064295 (Mm), NP_071798 (Rn)
UniProtKB P48775 (Hs), P48776 (Mm), P21643 (Rn)
Wikipedia TDO2 (Hs)
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

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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

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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 19/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=2887.