Tryptophan 2,3-dioxygenase (TDO) (TDO)

Tryptophan 2,3-dioxygenase (TDO) is a heme-dependent cytosolic enzyme that catalyzes the first and rate-limiting step of the kynurenine pathway, converting L-tryptophan into N-formyl-L-kynurenine (UniProt [2], Wikipedia [5]). Primarily expressed in the liver, TDO plays a crucial role in regulating systemic tryptophan levels and maintaining immune homeostasis (MDPI [4], PMC [15]). In the context of oncology, many tumors overexpress TDO to deplete local tryptophan and produce immunosuppressive kynurenine metabolites, thereby evading the host's immune system (Frontiers [13], PMC [14]). Beyond cancer, TDO is implicated in neurodegenerative and psychiatric disorders, where its activity influences the balance of neuroactive metabolites and serotonin levels in the brain (Expert Opin Ther Targets [9], PMC [12]). Therapeutic strategies focus on developing small-molecule TDO inhibitors, often as part of combination immunotherapies, to restore anti-tumor immunity or alleviate neurological symptoms (PubMed [1], PMC [8]). While several selective and dual IDO/TDO inhibitors are in development, challenges include achieving high selectivity and managing potential safety concerns related to altered serotonin metabolism (PubMed [1], Expert Opin Ther Targets [11]).

Other names

TDO2Tryptophan pyrrolaseTryptophan oxygenaseTryptamin 2,3-dioxygenaseTRPOTOHYPTRPTryptophanase

Inhibition of the oxidative cleavage of L-tryptophan to N-formyl-L-kynurenine, thereby preventing the production of immunosuppressive metabolites and restoring anti-tumor immune responses (MDPI [4], PMC [8]).