3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O'PROTAC

In this study, we identified 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O'PROTAC for degradation of the ERG transcription factor. This phthalic acid-based O'PROTAC presented an efficacy in degrading ERG comparable to those displayed by pomalidomide-based ERG O'PROTACs. Moreover, phthalic acid-being more chemically stable and economical than classical immunomodulatory drugs (IMiDs)-represents, as a ligand, a new alternative for the development of PROTACs, especially O'PROTACs.

Automated summary

In this study, a new ligand of cereblon (CRBN) E3 ubiquitin ligase, 3-aminophthalic acid, was identified and a phthalic acid-based O'PROTAC was developed for degradation of the ERG transcription factor. This phthalic acid-based O'PROTAC exhibited comparable efficacy in degrading ERG to pomalidomide-based ERG O'PROTACs. Moreover, phthalic acid, being more chemically stable and economical than classical immunomodulatory drugs (IMiDs), represents a new alternative as a ligand for the development of PROTACs, especially O'PROTACs.