ReviewNature reviews. Drug discovery2026
Safety considerations for cereblon-recruiting targeted protein degraders.
Review in Nature reviews. Drug discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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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
2 citing papers in PubMed.
- Evolving CRBN ligands enhance the drug-like properties of protein degraders.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- Flexible molecular chameleons: structural adaptability and therapeutic applications.Frontiers in chemistry · 2026Review
Corrections and comments
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Authors and funding
23 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted protein degraders (TPDs) that recruit the E3 ligase cereblon (CRBN) include two innovative drug classes: molecular glue degraders and proteolysis targeting chimeras. These TPDs have shown great promise in addressing difficult drug targets in oncologic and non-oncologic diseases; however, as well as inducing proteosomal degradation of their therapeutic target, they can also lead to degradation of unintended CRBN neosubstrates. This is a major safety consideration because many CRBN-recruiting TPDs are structurally related to thalidomide and other immunomodulatory imide drugs that are known to be teratogenic. The teratogenic effect of immunomodulatory imide drugs is due in part to their induction of CRBN-mediated neosubstrate degradation. Therefore, there is a need for a scientific consensus on rigorous, consistent and effective methods to assess the safety of CRBN-recruiting TPDs. Here, we provide an overview of the endogenous functions and substrates of CRBN as well as of the role of CRBN as the effector of immunomodulatory imide drugs, next-generation molecular glue degraders and proteolysis targeting chimeras. We discuss how degradation of unintended 'off-target' CRBN neosubstrates could potentially cause toxicity or safety liabilities in multiple organ systems as well as induce teratogenic effects. We outline key safety considerations for the development of CRBN-recruiting TPDs and suggest best practices for monitoring on-target versus off-target degradation.
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42009768What OpenQuestion holds
Registered trials
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