Replacing the phthalimide core in thalidomide with benzotriazole

Krasavin, M; Bubyrev, A; Kazantsev, A; Heim, C; Maiwald, S; Zhukovsky, D; Dar'in, D; Hartmann, MD; Brunev, A

doi:10.1080/14756366.2021.2024525

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Replacing the phthalimide core in thalidomide with benzotriazole

Krasavin, M., Bubyrev, A., Kazantsev, A., Heim, C., Maiwald, S., Zhukovsky, D., et al. (2022). Replacing the phthalimide core in thalidomide with benzotriazole. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), 527-530. doi:10.1080/14756366.2021.2024525.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000A-3755-9 Version Permalink: https://hdl.handle.net/21.11116/0000-000B-B39E-9

Genre: Journal Article

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Creators:
Krasavin, M, Author
Bubyrev, A, Author
Kazantsev, A, Author
Heim, C^{1, 2}, Author
Maiwald, S^{1, 2}, Author
Zhukovsky, D, Author
Dar'in, D, Author
Hartmann, MD^{1, 2}, Author
Brunev, A, Author

Affiliations:
1Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3375791
2Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society, ou_3477392

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Abstract: The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4ACRBN E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.

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Dates: Date issued: 2022-12

Publication Status: Issued

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Identifiers: DOI: 10.1080/14756366.2021.2024525
PMID: 35220840

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Title: Journal of Enzyme Inhibition and Medicinal Chemistry

Other : J. Enzym. Inhib. Med. Chem.

Source Genre: Journal

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Publ. Info: Basingstoke, UK : Taylor & Francis

Pages: - Volume / Issue: 37 (1) Sequence Number: - Start / End Page: 527 - 530 Identifier: ISSN: 1475-6366
CoNE: https://pure.mpg.de/cone/journals/resource/954925626348