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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.

SUBMITTER: Yan Y

PROVIDER: S-EPMC10467047 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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

Yan Yuqian Y Shao Jingwei J Ding Donglin D Pan Yunqian Y Tran Phuc P Yan Wei W Wang Zhengyu Z Li Hong-Yu HY Huang Haojie H

Chemical communications (Cambridge, England) 20220215 14

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 ...[more]

PMID: 35080528

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