Indoleamine 2,3-dioxygenase 1 (IDO1) and Tryptophan 2,3-dioxygenase (TDO) (IDO1, TDO)

Indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the first and rate-limiting step in the degradation of the essential amino acid tryptophan along the kynurenine pathway. This process leads to depletion of tryptophan and accumulation of immunosuppressive metabolites such as kynurenine. IDO1 is broadly inducible by inflammatory stimuli (e.g., interferon-gamma) and is expressed in multiple cell types including dendritic cells and various tumors, playing a crucial role in regulating immune responses and promoting tumor immune escape. TDO is constitutively expressed primarily in the liver and has a more limited tissue distribution, but also contributes to systemic tryptophan metabolism and immune regulation. Both have been implicated in the pathogenesis of cancer, neurodegenerative disorders, infection, and inflammation, and are actively pursued as drug targets, particularly in oncology for reversal of tumor immunosuppression.

Other names

Indoleamine-pyrrole 2,3-dioxygenaseINDOIDOTryptophan dioxygenaseTOTDO2

Enzyme inhibition (blockade of substrate—tryptophan—catabolism to limit immunosuppressive metabolite production); Restoration of anti-tumor immune responses by reducing kynurenine-mediated T cell suppression.