W-0019482

W-0019482 is a small molecule inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), an enzyme that plays a critical role in tumor-mediated immunosuppression by depleting tryptophan and increasing kynurenine levels in the tumor microenvironment. Identified as a lead compound from the Walter and Eliza Hall Institute (WEHI) library, W-0019482 exhibits potent activity in cell-based assays with an IC50 of approximately 80 nM against human IDO1. Preclinical studies in syngeneic mouse models of glioma (GL261) have demonstrated that systemic administration of W-0019482 reduces kynurenine-to-tryptophan ratios in both plasma and tumor tissue, leading to significant inhibition of tumor growth. Interestingly, the compound shows significantly greater potency in cell-based assays compared to cell-free enzymatic assays, suggesting efficient intracellular accumulation. W-0019482 serves as a chemical scaffold for the development of next-generation selective IDO1, selective TDO2, and dual IDO1/TDO2 inhibitors.