{"entity":{"id":"cereblon","kind":"target","name":"Cereblon (CRBN)","aka":[],"tldr":"The protein that lenalidomide and pomalidomide latch onto. Bound drug changes which proteins the cell tags for destruction, degrading the myeloma transcription factors Ikaros and Aiolos.","summary":"Cereblon is the substrate receptor of the CRL4 E3 ubiquitin ligase. Thalidomide, lenalidomide and pomalidomide act as molecular glues: bound to cereblon they recruit new substrates, above all the lymphoid transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos), for ubiquitination and destruction, which kills myeloma cells and stimulates T and natural killer cells. In del(5q) myelodysplastic syndrome lenalidomide degrades casein kinase 1 alpha instead. This mechanism founded the field of targeted protein degradation and is the template for molecular glue degraders.","asOf":"2026-09-04","wikipedia":"https://en.wikipedia.org/wiki/Cereblon","links":[{"label":"UniProt Q96SW2: CRBN","url":"https://www.uniprot.org/uniprotkb/Q96SW2/entry"}],"tags":[],"related":[],"cancers":["multiple-myeloma","mds"],"sections":[],"technologies":["celmods"],"targets":[],"drugs":["lenalidomide","pomalidomide"],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"symbol":"CRBN","role":[],"sources":[],"specificity":"broadly-expressed","distribution":"few-types","specificityNote":"Broadly expressed or essential: HPA finds the RNA at low tissue specificity; the 2 medicines aimed at it (Lenalidomide, Pomalidomide) act on the wild-type protein, so normal tissue is exposed and the therapeutic window comes from the tumour's faster division or its dependence on the protein. HPA CRBN: RNA low tissue specificity; high antibody staining in 21 normal tissues; highest cancer staining melanoma (1 of 11 high). Distribution: 2 cancer families in the corpus carry a prevalence row, label threshold or catalogue link for it (Multiple myeloma, Myeloid neoplasms); Open Targets associates it with 4 specific cancer types at or above 0.5 (plasma cell myeloma, myelodysplastic syndrome, follicular lymphoma, mantle cell lymphoma). (Rule 7 of scripts/fetch-target-specificity.ts.)","specificitySources":[{"label":"Human Protein Atlas CRBN tissue","url":"https://www.proteinatlas.org/ENSG00000113851-CRBN/tissue","note":"RNA tissue and blood lineage specificity, normal tissue antibody staining (version 25.1, CC BY-SA 3.0)"},{"label":"Open Targets ENSG00000113851 associations","url":"https://platform.opentargets.org/target/ENSG00000113851/associations","note":"cancer associations at or above 0.5 (CC0)"}],"hgnc":"HGNC:30185","ensembl":"ENSG00000113851","uniprot":"Q96SW2","entrez":"51185","firstDescribed":2000,"firstDescribedBasis":"sequence","firstDescribedNote":"Earliest sequence paper UniProt cites for the protein: Hu R.-M. et al, Proc. Natl. Acad. Sci. U.S.A, 2000, \"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/10931946/","biology":"Substrate receptor of the CRL4 (CUL4, DDB1, RBX1) E3 ubiquitin ligase; immunomodulatory drugs redirect it to degrade IKZF1, IKZF3 and CK1 alpha.","whereFound":["Multiple myeloma","Myelodysplastic syndrome with del(5q)"],"targetClass":"other","prevalence":[{"cancerId":"multiple-myeloma","pct":"nearly all","measure":"Cereblon expression at diagnosis; required for lenalidomide and pomalidomide activity, lost in a minority of refractory disease","source":"https://doi.org/10.1182/blood-2011-05-356063"}]},"route":"/targets/cereblon/","neighbours":{"cancer":[{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"mds","kind":"cancer","name":"Myelodysplastic syndromes / neoplasms (MDS)","route":"/cancers/mds/"},{"id":"myeloma-transplant-eligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-eligible","route":"/cancers/myeloma-transplant-eligible/"},{"id":"myeloma-transplant-ineligible","kind":"cancer","name":"Newly diagnosed multiple myeloma, transplant-ineligible","route":"/cancers/myeloma-transplant-ineligible/"},{"id":"myeloma-relapsed-refractory","kind":"cancer","name":"Relapsed or refractory multiple myeloma","route":"/cancers/myeloma-relapsed-refractory/"}],"technology":[{"id":"celmods","kind":"technology","name":"Cereblon E3 ligase modulators (CELMoDs)","route":"/technologies/celmods/"}],"drug":[{"id":"lenalidomide","kind":"drug","name":"Lenalidomide","route":"/drugs/lenalidomide/"},{"id":"pomalidomide","kind":"drug","name":"Pomalidomide","route":"/drugs/pomalidomide/"}],"term":[{"id":"del5q","kind":"term","name":"del(5q) (5q- syndrome and lenalidomide response)","route":"/terms/del5q/"}],"target":[{"id":"ikzf1","kind":"target","name":"IKZF1 (Ikaros)","route":"/targets/ikzf1/"},{"id":"ikzf3","kind":"target","name":"IKZF3 (Aiolos)","route":"/targets/ikzf3/"}]}}