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The alkylation of 4-hydroxythalidomide with tert-butyl bromoacetate to obtain a carboxylic acid derivative in order to facilitate the binding to the amine-terminal linker, for example, was carried out by Lis group in order to synthesize different cereblon-based PROTACs promoting the degradation of the 20S proteasome subunit 5

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Mechanistic studies confirmed its ability to restore PHB2 phosphorylation dynamics while maintaining cytoskeletal integrity, thereby outperforming conventional administration routes in terms of both therapeutic precision and duration

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