Hsp-targeting Chimeras (Hsp 靶向嵌合体)

Hsp-targeting Chimeras (HspTACs) represent a small-molecule targeted protein degradation platform based on heat shock proteins (Hsp). By conjugating a ligand for a protein of interest (POI) with an Hsp ligand, HspTACs harness the chaperone function of Hsp to mediate protein degradation via either the ubiquitin-proteasome system or the endosomal-lysosomal pathway. Furthermore, HspTACs capitalize on the characteristic overexpression of Hsp70 or Hsp90 in tumor cells; this feature promotes their preferential accumulation within these cells, thereby enabling tumor-selective degradation of the target protein (POI) specifically within Hsp-abundant tumor cells.