(S)-ACE-OH

(S)-ACE-OH is a small molecule metabolite of the phenothiazine sedative acepromazine that functions as a molecular glue to facilitate targeted protein degradation (TPD). It specifically recruits the E3 ubiquitin ligase TRIM21 to the multimeric Nuclear Pore Complex (NPC) protein NUP98. This recruitment triggers the selective ubiquitination and proteasomal degradation of multimeric NPC assemblies while sparing monomeric proteins, a selectivity profile attributed to the unique multimer-dependent activation mechanism of TRIM21. Beyond its activity as a molecular glue, (S)-ACE-OH has been utilized as a ligand to develop TRIM21-engaging PROTACs, offering a novel therapeutic platform for targeting pathologic protein aggregates, biomolecular condensates, and oncoproteins involved in cancer. The discovery of (S)-ACE-OH establishes TRIM21 as a viable E3 ligase for the selective elimination of diseased-associated protein complexes.

Other names

(S)-hydroxy-acepromazine(S)-1-(10-(3-(dimethylamino)propyl)-10H-phenothiazin-2-yl)ethanol(S)-2-(1-hydroxyethyl)promazine