ArticleChembiochem : a European journal of chemical biology2023
A Modular Chemistry Platform for the Development of a Cereblon E3 Ligase-Based Partial PROTAC Library.
Article in Chembiochem : a European journal of chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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7 citing papers in PubMed, 9 citations in OpenAlex.
- Integrated computational screen and validation of thalidomide-based PROTACs targeting SARS-CoV-2 main protease.RSC medicinal chemistry · 2026Article
- Article
- Synthesis, biological evaluation and clinical trials of Cereblon-based PROTACs.Communications chemistry · 2025Review
- Challenges in predicting PROTAC-mediated protein-protein interfaces with AlphaFold reveal a general limitation on small interfaces.Bioinformatics advances · 2025Article
- Proteolysis-targeting vaccines (PROTAVs) for robust combination immunotherapy of melanoma.bioRxiv : the preprint server for biology · 2024Article
- Anhydrous and Stereoretentive Fluoride-Enhanced Suzuki-Miyaura Coupling of Immunomodulatory Imide Drug Derivatives.The Journal of organic chemistry · 2024Article
- Development of Phenyl-substituted Isoindolinone- and Benzimidazole-type Cereblon Ligands for Targeted Protein Degradation.Chembiochem : a European journal of chemical biology · 2024Article
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8 authors at 1 institution in 1 country.
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Abstract
Proteolysis targeting chimeras (PROTACs) are a promising therapeutic strategy to selectively promote the degradation of protein targets by exploiting the ubiquitin-proteasome system. Among the limited number of E3 ligase ligands discovered for the PROTAC technology, ligands of cereblon (CRBN) E3 ligase, such as pomalidomide, thalidomide, or lenalidomide, are the most frequently used for the development of PROTACs. Our group previously reported that a phenyl group could be tolerated on the C4-position of lenalidomide as the ligand of CRBN to develop PROTACs. Herein, we report a modular chemistry platform for the efficient attachment of various ortho-, meta-, and para-substituted phenyls to the C4-position of the lenalidomide via Suzuki cross-coupling reaction, which allows the systematic investigation of the linker effect for the development of PROTACs against any target. We examined the substrate scope by preparing twelve lenalidomide-derived CRBN E3 ligase ligands with different linkers.
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