ReviewJournal of enzyme inhibition and medicinal chemistry2026
Evolving CRBN ligands enhance the drug-like properties of protein degraders.
Review in Journal of enzyme inhibition and medicinal chemistry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Proteolysis-targeting chimaeras (PROTACs) enable event-driven degradation of disease-relevant proteins by hijacking the ubiquitin-proteasome system (UPS). Cereblon (CRBN) is the most widely exploited recruiter due to its well-characterised binding pocket and strong clinical precedent from immunomodulatory imide drugs (IMiDs). However, early CRBN ligands have suboptimal pharmacokinetics, off-target neosubstrate degradation, immunomodulatory liabilities, and resistance mechanisms, which restrict the drug-like properties of CRBN-based degraders. This review systematically summarises CRBN ligand evolution and how chemical innovations improved PROTAC drug-likeness. We discuss classical IMiD-based ligands and their clinical translation, followed by next-generation recruiters, including non-IMiD scaffolds, conformationally constrained tricyclic and spirocyclic ligands, cyclic imides, covalent ligands, and stimuli-responsive designs. We highlight expanding application of novel CRBN ligands in molecular glue degrader development. Finally, key challenges and future directions for achieving selective, durable, and clinically viable CRBN-mediated protein degradation are discussed.
Indexed as
Identifiers
What Socratic holds
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 Socratic graph.