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These findings demonstrate that minimal structural alteration permits precision control over degrader target selectivity, while furnishing selective chemical probes for NSD2 and GSPT1.
The escalating global burden of metabolic diseases including obesity, type 2 diabetes, and metabolic dysfunction-associated fatty liver disease (MAFLD)-highlights an urgent need to identify new therapeutic targets. Although elevated hepatic de novo lipogenesis (DNL) is a hallmark of metabolic dysfunction, targeting i...
Molecular editing, rooted in synthetic chemistry, has emerged as a powerful tool for structure optimization in medicinal chemistry but remains underutilized in targeted protein degradation. Here, we demonstrate the utility of molecular editing by repurposing the NSD2 degrader LLC0424 with GSPT1 neosubstrate engagement...
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