Indoleamine 2,3-dioxygenase 2 (IDO2)

Indoleamine 2,3-dioxygenase 2 (IDO2) is a mammalian, cytosolic, heme-containing enzyme that catalyzes the first and rate-limiting step in the catabolism of the essential amino acid tryptophan along the kynurenine pathway. Like its paralog IDO1, IDO2 participates in the immune modulation by depleting tryptophan and producing metabolites that can suppress immune cell activity, which is relevant in cancer and chronic inflammation. IDO2 and IDO1 share similar reaction mechanisms but have distinct tissue expression profiles, substrate specificities, and may have partially redundant functions. Due to its role in immune evasion, especially in the tumor microenvironment, IDO2 has emerged as a potential therapeutic target for cancer immunotherapy; inhibitors targeting this enzyme or the broader IDO pathway are under clinical investigation.

Other names

Indoleamine 2,3-dioxygenase-2INDOL1Proto-indoleamine 2,3-dioxygenaseProto-IDO

Competitive or noncompetitive inhibition of tryptophan binding (small molecules or analogs interfere with substrate access to the heme active site) Blockade of enzymatic cleavage of the tryptophan indole ring (prevents local immunosuppression by blocking kynurenine pathway activity)