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

Abstract

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.