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• W3112793670 abstract "Through structural modification of an oxalamide derived chemotype, a novel class of highly potent, orally bioavailable IDO1-specific inhibitors was identified. Representative compound 18 inhibited human IDO1 with IC50 values of 3.9 nM and 52 nM in a cellular and human whole blood assay, respectively. In vitro assessment of the ADME properties of 18 demonstrated very high metabolic stability. Pharmacokinetic profiling in mice showed a significantly reduced clearance compared to the oxalamides. In a mouse pharmacodynamic model 18 nearly completely suppressed lipopolysaccharide-induced kynurenine production. Hepatocyte data of 18 suggest the human clearance to be in a similar range to linrodostat (1)." @default.
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• W3112793670 date "2021-02-01" @default.
• W3112793670 modified "2023-09-25" @default.
• W3112793670 title "Discovery of highly potent heme-displacing IDO1 inhibitors based on a spirofused bicyclic scaffold" @default.
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• W3112793670 doi "https://doi.org/10.1016/j.bmcl.2020.127738" @default.
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