ArticleNature communications2020
Structural bases of IMiD selectivity that emerges by 5-hydroxythalidomide.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 85 citations in OpenAlex.
- The synthetic landscape of cereblon (CRBN) binders: from thalidomide to emerging chemotypes.Chemical Society reviews · 2026Review
- Proteome-wide identification of the druggable CRBN interactome.Nature biotechnology · 2026Article
- Safety considerations for cereblon-recruiting targeted protein degraders.Nature reviews. Drug discovery · 2026Review
- Binding Modes of Thalidomide Derivatives in Cereblon-Neosubstrate Complexes Revealed by Molecular Dynamics and Free Energy Calculations.ACS omega · 2026Article
- Drug Discovery of Allosteric Molecular Glue Degraders (aMGDs): Expanding the Landscape of Targeted Protein Degradation.Journal of medicinal chemistry · 2026Article
- Fluorinated Aminopiperidones as Non-Glutarimide Thalidomide Analogs: Stereodivergent Synthesis and Validation.ChemMedChem · 2026Article
- Methods to Study the Molecular Mechanism and Drive the Design of Protein Degraders.Chemical reviews · 2026Review
- Research Progress of PROTACs in Breast Cancer: Subtype-Oriented Target Landscape, Clinical Stratification Evidence, and Engineering Strategies for Translation.Biomedicines · 2026Review
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.Journal of chemical information and modeling · 2026Article
- Understanding the Role of H-Bonds in the Stability of Molecular Glue-Induced Ternary Complexes.Journal of chemical information and modeling · 2026Article
- Orthogonal IMiD-Degron Pairs Induce Selective Protein Degradation in Cells.ACS chemical biology · 2025Article
- GlueFinder: A Data-Driven Framework for the Rational Discovery of Molecular Glues.bioRxiv : the preprint server for biology · 2025Article
- In-cell proximity target validation methods for heterobifunctional molecules with CRBN- or VHL-binder using AirID.Communications biology · 2025Article
- Advancements in Proteolysis Targeting Chimeras for Targeted Therapeutic Strategies in Alzheimer's Disease.Molecular neurobiology · 2025Review
- Unveiling the hidden interactome of CRBN molecular glues.Nature communications · 2025Article
- E3Docker: a docking server for potential E3 binder discovery.Nucleic acids research · 2025Article
- Targeting neuroinflammation: 3-monothiopomalidomide a new drug candidate to mitigate traumatic brain injury and neurodegeneration.Journal of biomedical science · 2025Article
- Thalidomide-induced limb malformations: an update and reevaluation.Archives of toxicology · 2025Review
- Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC.bioRxiv : the preprint server for biology · 2025Article
- Cell-type specific, inducible and acute degradation of targeted protein in mice by two degron systems.Nature communications · 2024Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thalidomide and its derivatives exert not only therapeutic effects as immunomodulatory drugs (IMiDs) but also adverse effects such as teratogenicity, which are due in part to different C2H2 zinc-finger (ZF) transcription factors, IKZF1 (or IKZF3) and SALL4, respectively. Here, we report the structural bases for the SALL4-specific proteasomal degradation induced by 5-hydroxythalidomide, a primary thalidomide metabolite generated by the enzymatic activity of cytochrome P450 isozymes, through the interaction with cereblon (CRBN). The crystal structure of the metabolite-mediated human SALL4-CRBN complex and mutagenesis studies elucidate the complex formation enhanced by the interaction between CRBN and an additional hydroxy group of (S)-5-hydroxythalidomide and the variation in the second residue of β-hairpin structure that underlies the C2H2 ZF-type neo-morphic substrate (neosubstrate) selectivity of 5-hydroxythalidomide. These findings deepen our understanding of the pharmaceutical action of IMiDs and provide structural evidence that the glue-type E3 ligase modulators cause altered neosubstrate specificities through their metabolism.
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