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- W4308253407 abstract "Abstract The identification of biologically active target compounds and their binding proteins is important in mechanism‐of‐action studies for drug development. Additionally, the newly discovered binding proteins provide unforeseen ideas for novel drug discovery and for subsequent structural transformation to improve target specificity. Based on the lead and final candidate compounds related to the type 5 phosphodiesterase (PDE5) inhibitor E4021, we designed chemical probes and identified their target proteins by the affinity chromatography approach. Aldehyde dehydrogenase family 1 member A3 (ALDH1A3), currently reported as a cancer stem cell target, was clearly isolated as a binding protein of the lead ‘immature’ inhibitor probe against PDE5. In the early derivatization to the closely related structure, Compound 5 (ER‐001135935) was found to significantly inhibit ALDH1A3 activity. The discovery process of a novel ALDH1A3‐selective inhibitor with affinity‐based binder identification is described, and the impact of this identification method on novel drug discovery is discussed." @default.
- W4308253407 created "2022-11-09" @default.
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- W4308253407 date "2022-11-25" @default.
- W4308253407 modified "2023-10-17" @default.
- W4308253407 title "Identification of a novel ALDH1A3‐selective inhibitor by a chemical probe with unrelated bioactivity: An approach to affinity‐based drug target discovery" @default.
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- W4308253407 doi "https://doi.org/10.1111/cbdd.14176" @default.
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