ArticleNature communications2026
A dihydrouracil CRBN ligand mitigates IMiD associated safety liabilities in heterobifunctional targeted protein degrader.
Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
3 citing papers in PubMed.
- Design, Synthesis, Biological Studies and Putative Binding Mode of Novel Benzotriazolothalidomide Derivatives as Cereblon Ligands.Chemical biology & drug design · 2026Article
- A unified platform for the rapid assembly of glutarimides for Cereblon E3 ligase modulatory drugs.Nature communications · 2026Article
- Targeted protein degradation dismantles undruggable targets to reverse immune evasion and therapy resistance in cancer.Frontiers in immunology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
40 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunomodulatory imide drugs (IMiDs) like lenalidomide and pomalidomide are effective in treating multiple myeloma (MM) but pose hematotoxicity risks by degrading neosubstrates Ikaros (IKZF1) and Aiolos (IKZF3). When these IMiD scaffolds are integrated into proteolysis targeting chimeras (PROTACs), they can inadvertently lead to the degradation of these neosubstrates alongside the intended protein of interest (POI), raising safety concerns. This study profiles existing PROTACs and reveals instances of undesired degradation of IMiD-associated neosubstrates. We have developed in vitro hematopoietic assays to scrutinize the IMiD effects and describe the mechanistic insights on cell differentiation rewiring towards megakaryocytes together with an activation of the interferon response that is phenocopied by an Ikaros knock-out model. Moreover, we have identified a CRBN ligand that mitigates these safety liabilities and can be effectively incorporated into PROTACs. This advancement provides a promising path toward safer preclinical development of PROTACs, especially as the field expands into chronic disease treatments beyond oncology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.