# Cereblon E3 ligase modulators (CELMoDs)

Source: https://onco.cc/technologies/celmods/  
OnCo record `celmods` (Technology). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Next-generation relatives of lenalidomide that make the cell's disposal machinery destroy the myeloma proteins Ikaros and Aiolos more completely, working after older drugs fail.

## Summary

Thalidomide, lenalidomide and pomalidomide act by binding cereblon and redirecting it to degrade Ikaros and Aiolos. Cereblon E3 ligase modulators (iberdomide, mezigdomide) bind cereblon more tightly and degrade these targets faster and more deeply, producing responses in myeloma refractory to lenalidomide and pomalidomide in phase 1 and 2 trials; phase 3 trials with dexamethasone and antibodies are under way. Neutropenia is the main toxicity.

## Fields

- Kind: Technology
- Status: phase-3
- Last checked: 2026-09-04
- Principle: Molecular glues bind cereblon and reshape its surface so that transcription factors Ikaros and Aiolos are ubiquitinated and degraded, killing plasma cells and stimulating T cells.
- Strengths: Active after lenalidomide and pomalidomide failure; Oral; Immune-stimulating effects add to antibody partners
- Limitations: Neutropenia; Not yet approved; Resistance through cereblon loss

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Cereblon
- Wikipedia: https://en.wikipedia.org/wiki/Cereblon

## Connected records

- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Relapsed or refractory multiple myeloma](https://onco.cc/cancers/myeloma-relapsed-refractory/)
- fronts: [Targeted Therapy](https://onco.cc/fronts/targeted-therapy/)
- targets: [Cereblon (CRBN)](https://onco.cc/targets/cereblon/), [IKZF1 (Ikaros)](https://onco.cc/targets/ikzf1/), [IKZF3 (Aiolos)](https://onco.cc/targets/ikzf3/), [IRF4](https://onco.cc/targets/irf4/)
- drugs: [Iberdomide](https://onco.cc/drugs/iberdomide/), [Mezigdomide](https://onco.cc/drugs/mezigdomide/)
- technologies: [Molecular glue discovery platforms](https://onco.cc/technologies/molecular-glue-platforms/)
- trials: [A Study to Compare Iberdomide Maintenance Versus Lenalidomide Maintenance Therapy Following Autologous Stem Cell Transplant in Participants With Newly](https://onco.cc/trials/nct05827016/), [A Study to Determine Dose, Safety, Tolerability and Efficacy of CC-220 Monotherapy, and in Combination With Other Treatments in Subjects With Multiple](https://onco.cc/trials/nct02773030/), [A Study to Determine the Recommended Dose and Regimen and to Evaluate the Safety and Preliminary Efficacy of CC-92480 in Combination With Standard Tre](https://onco.cc/trials/nct03989414/), [A Study to Determine the Recommended Dose and Schedule, and Evaluate the Safety and Preliminary Efficacy of Mezigdomide in Combination With Elranatama](https://onco.cc/trials/nct06988488/), [A Study to Evaluate Mezigdomide in Combination With Carfilzomib and Dexamethasone (MeziKD) Versus Carfilzomib and Dexamethasone (Kd) in Participants W](https://onco.cc/trials/nct05552976/), [A Study to Evaluate Mezigdomide, Bortezomib and Dexamethasone (MEZIVd) Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) in Participants With Re](https://onco.cc/trials/nct05519085/), [A Study to Evaluate Safety, Drug Levels and Effectiveness of CC-92480 (BMS-986348) in Combination With Other Treatments in Participants With Relapsed ](https://onco.cc/trials/nct05372354/), [Open-label Study Comparing Iberdomide, Daratumumab and Dexamethasone (IberDd) Versus Daratumumab, Bortezomib, and Dexamethasone (DVd) in Participants ](https://onco.cc/trials/nct04975997/)

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