IDO1/TDO dual inhibitor RY103 targets Kyn-AhR pathway and exhibits preclinical efficacy on pancreatic cancer.

Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzing the conversion of tryptophan (Trp) to kynurenine (Kyn) in kynurenine pathway (KP) is involved in the immunosuppression in pancreatic cancer (PC), but the value of IDO1 as an independent prognostic marker for PC is uncertain. Moreover, the correlation between tryptophan 2,3-dioxygenase (TDO), an isozyme of IDO1, and PC is largely unknown. Using TCGA database, the correlation between IDO1 and/or TDO expression and PC patients' survival was analyzed.

Evaluation and comparison of the commonly used bioassays of human indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO).

Inhibitors of indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are potential drugs for the treatment of tumor and neurological diseases. A variety of bioassays have been developed to evaluate IDO1/TDO (IDO1 and/or TDO) inhibitors, with uncertainty regarding how the differences in the assay methods or protocols may influence the assay outcomes. The enzymatic assays of IDO1/TDO are usually performed with NFK assay and Kyn adduct assay while the cellular assays of IDO1 are carried out with Hela assay and HEK293 assay.

Both IDO1 and TDO contribute to the malignancy of gliomas via the Kyn-AhR-AQP4 signaling pathway.

Indoleamine 2,3-dioxygenase 1 (IDO1), indoleamine 2,3-dioxygenase 2 (IDO2), and tryptophan 2,3-dioxygenase (TDO) initiate the first step of the kynurenine pathway (KP), leading to the transformation of L-tryptophan (Trp) into L-kynurenine (Kyn) and other downstream metabolites. Kyn is known as an endogenous ligand of the aryl hydrocarbon receptor (AhR). Activation of AhR through TDO-derived Kyn is a novel mechanism to support tumor growth in gliomas.

HS suppresses indoleamine 2, 3-dioxygenase 1 and exhibits immunotherapeutic efficacy in murine hepatocellular carcinoma.

Background: Over-expression and over-activation of immunosuppressive enzyme indoleamine 2, 3 -dioxygenase 1 (IDO1) is a key mechanism of cancer immune escape. However, the regulation of IDO1 has not been fully studied. The relation between hydrogen sulfide (HS) and IDO1 is unclear.