3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O'PROTAC. Issue 14 (26th January 2022)

• Record Type: Journal Article
• Authors: Yan, Yuqian; Shao, Jingwei; Ding, Donglin; Pan, Yunqian; Tran, Phuc; Yan, Wei; Wang, Zhengyu; Li, Hong-yu; Huang, Haojie
• Is Part Of: Chemical communications. Volume 58:Issue 14(2022)
• Page Start: 2383
• Page End: 2386
• Publication Date: 2022-01-26
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1039/d1cc06525d
• Languages: English
• ISSNs: 1359-7345

Abstract

Abstract : In this study, we discovered 3-aminophthalic acid as a new ligand of cereblon (CRBN) E3 ubiquitin ligase and developed a phthalic acid-based O'PROTAC for ERG destruction, expanding the pool of ligands for development of PROTACs, especially O'PROTACs. 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.