Indoleamine 2,3-dioxygenase 1 (IDO1) has attracted much attention in the field of cancer immunotherapy as an immunomodulatory enzyme. To identify potential IDO1 inhibitors, a novel series of compounds with N,N-diphenylurea and triazole structures were synthesized. The designed compounds underwent organic synthesis, and subsequent enzymatic activity experiments targeting IDO1 confirmed their activity at the molecular level. These experiments provided validation for the efficacy of the designed compounds in inhibiting IDO1, compound exhibited an IC value of 1.73 ± 0.97 μM. Further molecular docking study further explained the binding mode and reaction potential of compound with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases.
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http://dx.doi.org/10.3389/fchem.2023.1222825 | DOI Listing |
Exp Neurol
January 2025
Laboratory of Neurodegenerative Diseases and Neuroinjury Diseases, Wuxi, School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China; MOE Medical Basic Research Innovation Center for Gut Microbiota and Chronic Diseases, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu 214122, China. Electronic address:
Abnormal tryptophan metabolism is closely linked with neurological disorders. Research has shown that indoleamine 2,3-dioxygenase 1 (IDO-1), the first rate-limiting enzyme in tryptophan degradation, is upregulated in Parkinson's disease (PD). However, the precise role of IDO-1 in PD pathogenesis remains elusive.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 561113, China.
Astragalus membranaceus (AM) herb is a component of traditional Chinese medicine used to treat various cancers. Herein, we demonstrate a strong anti-leukemic effect of AM injected (Ai) into the mouse model of erythroleukemia induced by Friend virus. Chemical analysis combined with mass spectrometry of AM/Ai identified the compounds Betulinic acid, Kaempferol, Hederagenin, and formononetin, all major mediators of leukemia inhibition in culture and in vivo.
View Article and Find Full Text PDFiScience
December 2024
Department Gynecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu 610041, China.
Reprogramming tryptophan metabolism (TRP) may be able to overcome immunosuppression and restore the immune checkpoint blockade (ICB) response in patients with epithelial ovarian cancer (EOC) resistant to ICB therapy because TRP metabolism is involved in the kynurenine/indole and serotonin pathways of tryptophan metabolism. Herein, employing amitriptyline (AMI), an antagonist of TLR4 and serotonin transporter (SERT), we revealed that AMI remodels the immunological landscape of EOC. In particular, AMI lowered the expression of IDO1, IL-4I1, and PD-L1, the quantity of KYN and indoles, and the level of immunosuppressive immune cells MDSC, Tregs, and CD8CD39+/PD-1+ T cell.
View Article and Find Full Text PDFCancer Immunol Immunother
January 2025
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, China.
Microsatellite stable (MSS) colorectal cancer (CRC) is a subtype of CRC that generally exhibits resistance to immunotherapy, particularly immune checkpoint inhibitors such as PD-1 blockade. This study investigates the effects and underlying mechanisms of combining PD-1 blockade with IDO1 inhibition in MSS CRC. Bioinformatics analyses of TCGA-COAD and TCGA-READ cohorts revealed significantly elevated IDO1 expression in CRC tumors, correlating with tumor mutation burden across TCGA datasets.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
December 2024
Department of Chemistry, School of Science, Westlake University Institution Institute of Natural Sciences, Westlake Institute for Advanced Study, No. 600 Dunyu Road, Hangzhou, 310024, Zhejiang Province, China.
Indoleamine 2,3-dioxygenase 1 (IDO1) inhibitors are promising for treating tumors but have limited efficacy due to the immunosuppressive tumor microenvironment. In this study, we develop an orchestrated nanoparticle system using modular peptide assemblies, where the co-assembled sequences are designed for the specific binding to the hydrophobic and hydrophilic domains, guiding the assembly process and enabling the customization of nanoparticle properties. We exploit the modularity of this platform to integrate a hydrophobic ferroptosis precursor, an IDO1 inhibitor, and a hydrophilic peptidic PD-L1 antagonist for optimizing therapeutic outcomes through ferroptosis-enhanced tumor immunotherapy.
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