HisTAC

HisTAC (polyHis-targeting chimera) is a ligand-independent targeted protein degradation (TPD) platform designed to degrade proteins of interest (POIs) that have been engineered with a polyhistidine tag. The system utilizes a nickel-nitrilotriacetic acid (Ni2+-NTA) moiety to bind the polyhistidine tag on the target protein and a separate ligand to recruit an E3 ubiquitin ligase, such as Cereblon (CRBN) or Von Hippel-Lindau (VHL). This proximity-induced approach facilitates the ubiquitination and subsequent proteasomal degradation of the tagged protein. HisTAC is particularly useful for studying traditionally undruggable targets or proteins lacking high-affinity small-molecule ligands, as it bypasses the need for a specific POI-binding ligand. It has demonstrated efficacy in degrading His-tagged versions of BRD4 and the RNA-binding protein PSPC1 in cellular models.

Other names

polyHis-targeting chimeraspolyhistidine-directed degraderpolyhistidine-targeting chimeras