Indoleamine 2,3-dioxygenase 1 and Tryptophan 2,3-dioxygenase (IDO1, TDO, TDO2)

Indoleamine 2,3-dioxygenase 1 (IDO1) is a cytosolic, heme-containing, monomeric enzyme that catalyzes the initial and rate-limiting step in the kynurenine pathway of tryptophan degradation: the oxidation of L-tryptophan to N-formylkynurenine. Tryptophan 2,3-dioxygenase (TDO, also TDO2) is a structurally distinct, heme-containing, tetrameric enzyme—primarily hepatic—that catalyzes the same biochemical reaction. Both IDO1 and TDO are crucial in immune regulation, suppressing T-cell proliferation and promoting immune tolerance, mechanisms exploited by tumors for immune escape. IDO1 is widely expressed in various tissues and induced under inflammation, while TDO is mainly expressed in the liver and maintains systemic tryptophan homeostasis. Increased activity of these enzymes is implicated in cancer progression, autoimmune diseases, infections, chronic inflammation, and neurodegenerative conditions, making them highly relevant therapeutic targets in oncology and immunology. Numerous small molecule inhibitors, especially of IDO1, have been developed and are under clinical investigation for cancer immunotherapy.

Other names

IDO1INDOIndoleamine-pyrrole 2,3-dioxygenaseTDOTDO2

Competitive or allosteric inhibition of tryptophan dioxygenase activity, preventing conversion of tryptophan to N-formylkynurenine. Immune de-repression: By blocking IDO1/TDO activity, these drugs restore T-cell proliferation, reduce immune tolerance in the tumor microenvironment, and enhance anti-tumor immunity.