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Heterobifunctional proteomimetic polymers for targeted degradation of MYC and KRAS - PubMed

4 hours ago
  • #Proteomimetic Polymers
  • #Biomedical Materials
  • #Targeted Protein Degradation
  • Introduction of HYDRAC (HYbrid DegRAding Copolymer), a polymeric platform for targeted protein degradation (TPD).
  • HYDRAC integrates target-binding peptides with peptide-based or small-molecule degrons for selective degradation of proteins like MYC and KRAS.
  • HYDRACs are synthetically scalable, structurally tunable, and support multivalent payload conjugation, enabling diverse target-binding and E3-ligase recruiter incorporation.
  • Demonstrated efficacy in degrading MYC and KRAS in vitro and achieving durable tumor suppression in murine models.
  • Potential for pan-KRAS degradation across multiple alleles using HYDRACs with consensus RAS-binding motifs.
  • Authors envision HYDRACs as a generalizable paradigm to expand the TPD toolkit.