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• W2111133339 abstract "Activation of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) underlies the course of several human pathological conditions and, to date, no efficacious therapeutic IDO inhibitors are available. We proposed to develop a robust screening system based on the use of yeast cells to identify new lead compounds for the pharmacological inhibition of IDO—the BLOCKADE platform. Yeast combines the advantages of a relevant surrogate model for eukaryotic cell processes with the amenity to miniaturization and automation. We brought added value to the system by increasing the stringency of our assay, as the BLOCKADE strain was not deleted for any efflux pump, thus creating additional challenges for test compounds to be identified as hits. Screening of a library of 50 080 small molecules led to the identification of 101 potential IDO inhibitors, a low hit rate of 0.2%, reflecting the stringent assay conditions imposed. Most important, secondary pharmacology assays in mammalian cells confirmed activity for 76% of the hits, whereas hepatotoxicity testing indicated that 87% of them displayed a safe profile. The high predictivity rates obtained using the BLOCKADE platform clearly validate our system as a powerful tool for drug discovery." @default.
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• W2111133339 date "2012-12-01" @default.
• W2111133339 modified "2023-10-06" @default.
• W2111133339 title "A Powerful Yeast-Based Screening Assay for the Identification of Inhibitors of Indoleamine 2,3-Dioxygenase" @default.
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• W2111133339 doi "https://doi.org/10.1177/1087057112452595" @default.
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