{"entity":{"id":"celmods","kind":"technology","name":"Cereblon E3 ligase modulators (CELMoDs)","aka":[],"tldr":"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.","status":"phase-3","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cereblon","links":[{"label":"Wikipedia","url":"https://en.wikipedia.org/wiki/Cereblon"}],"tags":[],"related":[],"cancers":["multiple-myeloma"],"sections":["targeted-therapy"],"technologies":[],"targets":["cereblon"],"drugs":["iberdomide","mezigdomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"notes":[],"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"]},"route":"/technologies/celmods/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"}],"section":[{"id":"targeted-therapy","kind":"section","name":"Targeted Therapy","route":"/fronts/targeted-therapy/"}],"target":[{"id":"cereblon","kind":"target","name":"Cereblon (CRBN)","route":"/targets/cereblon/"}],"drug":[{"id":"iberdomide","kind":"drug","name":"Iberdomide","route":"/drugs/iberdomide/"},{"id":"mezigdomide","kind":"drug","name":"Mezigdomide","route":"/drugs/mezigdomide/"}]}}