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

Yuqian Yan; Jingwei Shao; Donglin Ding; Yunqian Pan; Phuc Tran; Wei Yan; Zhengyu Wang; Hong Yu Li; Haojie Huang

doi:10.1039/d1cc06525d

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

Yuqian Yan, Jingwei Shao, Donglin Ding, Yunqian Pan, Phuc Tran, Wei Yan, Zhengyu Wang, Hong Yu Li, Haojie Huang

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

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.

Original language	English (US)
Pages (from-to)	2383-2386
Number of pages	4
Journal	Chemical Communications
Volume	58
Issue number	14
DOIs	https://doi.org/10.1039/d1cc06525d
State	Published - Feb 18 2022
Externally published	Yes

ASJC Scopus subject areas

Catalysis
Electronic, Optical and Magnetic Materials
Ceramics and Composites
Chemistry(all)
Surfaces, Coatings and Films
Metals and Alloys
Materials Chemistry

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title = "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.",

author = "Yuqian Yan and Jingwei Shao and Donglin Ding and Yunqian Pan and Phuc Tran and Wei Yan and Zhengyu Wang and Li, {Hong Yu} and Haojie Huang",

note = "Funding Information: This work was supported in part by the Mayo Clinic Foundation (to H. H.) and the ARA grant (to H.-Y. L.), and the National Institutes of Health (R01CA134514 and R01CA130908 to H. H. and R01CA197178 and R01CA249282 to H.-Y. L.). Publisher Copyright: {\textcopyright} 2022 The Royal Society of Chemistry.",

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doi = "10.1039/d1cc06525d",

language = "English (US)",

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T1 - 3-Aminophthalic acid, a new cereblon ligand for targeted protein degradation by O'PROTAC

AU - Yan, Yuqian

AU - Shao, Jingwei

AU - Ding, Donglin

AU - Pan, Yunqian

AU - Tran, Phuc

AU - Yan, Wei

AU - Wang, Zhengyu

AU - Li, Hong Yu

AU - Huang, Haojie

N1 - Funding Information: This work was supported in part by the Mayo Clinic Foundation (to H. H.) and the ARA grant (to H.-Y. L.), and the National Institutes of Health (R01CA134514 and R01CA130908 to H. H. and R01CA197178 and R01CA249282 to H.-Y. L.). Publisher Copyright: © 2022 The Royal Society of Chemistry.

PY - 2022/2/18

Y1 - 2022/2/18

N2 - 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.

AB - 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.

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SP - 2383

EP - 2386

JO - Chemical Communications

JF - Chemical Communications

IS - 14

ER -

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

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