Cereblon (CRBN)
Cereblon (CRBN) is an intracellular multifunctional protein that functions as a component of an E3 ubiquitin ligase system and cooperates with other elements of the ubiquitin–proteasome pathway.
Cereblon (CRBN) is an intracellular multifunctional protein that functions as a component of an E3 ubiquitin ligase system and cooperates with other elements of the ubiquitin–proteasome pathway. Its biological importance derives in part from its ability to bind immunomodulatory drugs such as lenalidomide and to participate in the selective ubiquitination and proteasomal degradation of recruited proteins. 42101529May42627009Aug
CRBN has become a central pharmacological target for targeted protein degradation. Cereblon-recruiting molecular glue degraders can promote degradation of proteins such as IKZF1, IKZF3, GSPT1, GSPT2, CK1α, and SCD, whereas CRBN-recruiting proteolysis-targeting chimeras (PROTACs) use a bifunctional design to bring CRBN-containing ligase machinery into proximity with a selected target. These mechanisms have been investigated in multiple myeloma, immune-cell regulation, cancer therapy, and drug-delivery development. 42118707May42149616May42051197Apr
Rebuilt from PubMed 18 Sept 2026 · no new papers today
Where the papers sit
10 papers study cereblon (crbn) directly. The themes below are drawn from those 10. 1 new direction follows.
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CRBN Ligand Design and Applications : CRBN ligand work spans binding characterization, PROTAC and prodrug design, radiolabeled imaging agents, and early biomarker evaluation. The field is broadening CRBN recruitment beyond therapy while clinical validation remains preliminary. 5 papers · 50%
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Molecular Glue Degrader Development : Molecular glue research is moving toward scalable discovery and systematic carcinogenicity assessment. ERα degradation through HSP27-associated E3 ligase recruitment offers a route around endocrine-resistant breast cancer. 3 papers · 30%
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CRBN-Mediated Protein Degradation : CRBN degraders are being applied to both BTK elimination and IKZF1/3 degradation. Mezigdomide links this strategy to restored cytokine production and reversal of T-cell exhaustion. 2 papers · 20%
CRBN is proposed as an early prognostic biomarker in paediatric sepsis
The paediatric sepsis prospective observational study protocol treats CRBN not as a component recruited by therapeutic degraders but as a measurable immune-related biomarker whose expression may predict disease trajectory and mortality in children with sepsis 42613111Aug. Whereas the other abstracts use CRBN chiefly as an intracellular binding partner or E3-ligase recruitment element for drug design and targeted protein degradation, this study gives it a clinical prognostic role in an acute infectious disease. If validated, that would shift CRBN from a pharmacological mechanism into a tool for early triage and outcome prediction.
Recent Findings on Cereblon (CRBN)
CRBN Translational Research: CRBN ligand engineering now connects structural characterization with radiolabeling, targeted protein degradation, and clinical biomarker development. The purified cereblon Thalidomide-Binding Domain retained lenalidomide binding, enabling NMR-based analysis of ligand interactions 42101529May. Bioorganometallic modification weakened CRBN binding, whereas [Re(η6-lena)2]+ retained measurable affinity and showed rapid blood clearance with predominant renal excretion in mice 42627009Aug. CRBN-recruiting PROTAC prodrugs used triazole quaternization, tertiary-amine alkylation, or hydroxyl-linker installation to control self-immolative release and cellular potency in multiple myeloma models 42554619Aug. C13p strengthened hFAAH–CRBN interactions through stepwise assembly, while hFAAH dissociated independently in most trajectories 42333818Jun. A prospective paediatric sepsis protocol will test whether CRBN mRNA and protein levels correlate with 28-day mortality, pSOFA scores, inflammation, and PICU outcomes 42613111Aug.
Molecular Glue Degraders: CRBN-based molecular glue discovery is moving toward scalable chemical assembly, phenotypic screening, and integrated safety assessment. A primary amine-based photoclick platform generated more than 1000 CRBN-centric molecules directly in multi-well plates and identified degraders of GSPT1, CK1α, and multiple targets 42149616May. Hydrophobic-tag degrader VI-10h used an ERα–HSP27–RING1 ternary complex to drive ERα proteasomal degradation and showed antitumor activity in endocrine-resistant breast cancer models 42189698May. Carcinogenicity assessment emphasizes the biological effects of the recruited E3 ubiquitin ligase alongside the primary target, while early-generation cereblon molecular glue degraders create challenges for translatability and traditional weight-of-evidence interpretation 42051197Apr. These findings support broader degrader screening while requiring compound-specific evaluation of E3-ligase biology and carcinogenicity risk.
CRBN-Based Protein Degradation: CRBN-mediated degradation is producing distinct therapeutic effects through BTK depletion and IKZF1/IKZF3 modulation. Novel CRBN-binding warheads enabled orally bioavailable BTK-targeting PROTACs that degraded wild-type and mutated BTK without concomitant activity against IKZF1, IKZF3, or GSPT1 42720469Sep. The lead compounds ISM-PR25 and ISM-PR44 showed subnanomolar BTK degradation in malignant B cells and degraded BTK in mouse circulating B cells after a single oral dose 42720469Sep. Mezigdomide instead targeted IKZF1 and IKZF3 simultaneously, reducing exhaustion-related markers and restoring proinflammatory cytokine expression in exhausted T cells 42118707May. Mezigdomide also enhanced target-cell killing with the BCMA-targeting T-cell engager alnuctamab, supporting combination treatment in multiple myeloma 42118707May.
Written from 10 PubMed abstracts, each one cited by PMID above. Published: 2026-08-29. Last written: 2026-09-12 by GPT. Drafted by language models from published abstracts; not medical advice.