Drug targets a biomolecule that can directly bind to drugs and then react. Generally, the target refers to a protein related to the cause of disease. The focus of the target began with focusing on tumors and then began to spread to various fields. Introduction to  INDO/IDO/IDO1 protein is a common target in medicine.

IDO 1 is a monomeric oxidase expressed at low levels in most tissues, containing a large C-terminal domain (CTD) and a small N-terminal domain (NTD). This gene encodes diamine 2,3-dioxygenase (ido), a heme enzyme that catalyzes the first and rate-limiting step of tryptophan breakdown into N-formyl-aminoininosine.

Fig 1: IDO1 Crystal structure (Reference documentation: Pallotta MT, Rossini S, Suvieri C, Coletti A, Orabona C, Macchiarulo A, Volpi C, Grohmann U. Indoleamine 2,3-dioxygenase 1 (IDO1): an up-to-date overview of an eclectic immunoregulatory enzyme. FEBS J. 2022 Oct;289(20):6099-6118.)

Under the action of IDO 1, the double bond at positions 2 and 3 of L-tryptophan is broken, producing the primary metabolite N-formylated canine urine (NFK) by canine urine, and then through a series of enzymatic reactions to generate a variety of active metabolites. IDO 1 produces a series of metabolites that inhibit iron death of oxidative cell death, and in an inflammatory setting, IDO 1 controls essential amino acid depletion, AhR activation, iron death inhibition, and biosynthesis of key metabolic intermediates. The IDO 1 protein contains two immune receptor tyrosine-based inhibitory motifs (ITIM) that trigger inhibitory signaling by binding to the PI3K p110 and SHP-1 proteins. This immunosuppressive activity was independent of the catalytic activity of IDO 1. KYN and its metabolite, canine retinoic acid (KYNA), are potent activators of the aromatics receptor (AhR) that enhance immunosuppression. IDO 1-KYN-AhR signaling counteracts excessive pro-inflammatory responses in acute inflammation, but in chronic inflammatory states, it has many detrimental effects. IDO 1 / TDO accounts for the release of Kyn, and Kyn activates the AhR to promote cell motility through the Kyn-AhR-AQP 4 signaling pathway in U87MG glioma cells. Suggesting that IDO 1 and TDO may be valuable therapeutic targets for glioma.