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- W4212854522 abstract "Abstract For the discovery of novel chemical matter generally endowed with bioactivity, strategies may be particularly efficient that combine previous insight about biological relevance, e.g., natural product (NP) structure, with methods that enable efficient coverage of chemical space, such as fragment‐based design. We describe the de novo combination of different 5‐membered NP‐derived N‐heteroatom fragments to structurally unprecedented “pseudo‐natural products” in an efficient complexity‐generating and enantioselective one‐pot synthesis sequence. The pseudo‐NPs inherit characteristic elements of NP structure but occupy areas of chemical space not covered by NP‐derived chemotypes, and may have novel biological targets. Investigation of the pseudo‐NPs in unbiased phenotypic assays and target identification led to the discovery of the first small‐molecule ligand of the RHO GDP‐dissociation inhibitor 1 (RHOGDI1), termed Rhonin. Rhonin inhibits the binding of the RHOGDI1 chaperone to GDP‐bound RHO GTPases and alters the subcellular localization of RHO GTPases." @default.
- W4212854522 created "2022-02-24" @default.
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- W4212854522 date "2022-03-02" @default.
- W4212854522 modified "2023-10-17" @default.
- W4212854522 title "The Pseudo‐Natural Product Rhonin Targets RHOGDI" @default.
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- W4212854522 doi "https://doi.org/10.1002/ange.202115193" @default.
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