(S)-ACE-OH

(S)-ACE‑OH is the active metabolite of Acepromazine, acting as a molecular glue degrader. (S)-ACE-OH induces functional interaction between TRIM21 and NUP98, promoting protein ubiquitination and degradation of TRIM21 at the nuclear pore complex. (S)-ACE-OH triggers nucleocytoplasmic transport disorder and exerts interferon-potentiated cytotoxic effects on certain cancer cells. (S)-ACE-OH can be used in cancer-related research ^[1].

In Vitro, (S)-ACE-OH (10-6-10-4 M; 3 days) reduces the viability of IFNγ-pretreated A549 and DLD-1 cells in a concentration-dependent manner, whereas its enantiomer (R)-ACE-OH shows no activity^[1]. (S)-ACE-OH (2-50 μM; 8 hours) induces concentration-dependent degradation of GLE1, SMPD4 and NUP35 in IFNγ-pretreated A549 cells^[1]. (S)-ACE-OH (0.5-15 μM; 30 minutes) acts as a molecular glue in vitro to induce a concentration-dependent interaction between TRIM21 (wild-type and D355A mutant) and NUP98APD^[1]. (S)-ACE-OH binds directly to the TRIM21D355A PRYSPRY domain with a Kd value of 17.9 μM, and promotes the formation of a high-affinity ternary complex between TRIM21D355A and NUP98APD; it triggers TRIM21D355A-mediated polyubiquitination of polymerized NUP98APD and related proteins in vitro^[1].

References:
[1]. Lu P, et al. Selective degradation of multimeric proteins by TRIM21-based molecular glue and PROTAC degraders. Cell. 2024 Dec 12;187(25):7126-7142.e20.