HGC652 is a molecular glue degrader targeting TRIM21 with a TRIM21-dependent nuclear membrane disruption effect. HGC652 binds to the PRY-SPRY domain of TRIM21 with high affinity ( K a =0.061 μM), mediates the interaction between TRIM21 and NUP98 , and redirects E3 ligase activity. By triggering the polyubiquitination and proteasomal degradation of nucleoporins (such as NUP155 and GLE1 ), HGC652 disrupts nuclear membrane integrity, alters nuclear morphology, induces genomic instability, and thereby induces cancer cell death.
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