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

• Published in: Cancer letters Vol. 522; pp. 32 - 43
• Main Authors: Liang, Heng, Li, Tianqi, Fang, Xin, Xing, Zikang, Zhang, Shengnan, Shi, Lei, Li, Weirui, Guo, Leilei, Kuang, Chunxiang, Liu, Hongrui, Yang, Qing
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.12.2021; Elsevier Limited
• Subjects: Animals; Antigens; Apoptosis; Cell Movement - drug effects; Cell Proliferation - drug effects; Cytochrome; Cytotoxicity; Disease Models, Animal; Enzyme Inhibitors - pharmacology; Enzymes; Gene Expression Regulation, Neoplastic - drug effects; Genomes; Humans; Hydrocarbons; Immunomodulation; Immunosuppression; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors; Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics; Kinases; Kynurenine - biosynthesis; Kynurenine pathway; Ligands; MDSCs; Metastasis; Mice; Neoplasm Invasiveness - genetics; Neoplasm Invasiveness - pathology; Organic Chemicals - pharmacology; Organic Chemicals - therapeutic use; Pancreatic cancer; Pancreatic Neoplasms; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Pheochromocytoma cells; Proteins; Receptors, Aryl Hydrocarbon - genetics; Signal Transduction - drug effects; T cells; Tryptophan; Tryptophan 2,3-dioxygenase; Tryptophan Oxygenase - antagonists & inhibitors; Tryptophan Oxygenase - genetics; Tumor immunosuppression; Tumor metastasis; MDSCs; Tumor immunosuppression; T cells; Kynurenine pathway; Tumor metastasis

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 b...