Loading
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.
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.
In plain words · 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.
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.
Substrate receptor of the CRL4 (CUL4, DDB1, RBX1) E3 ubiquitin ligase; immunomodulatory drugs redirect it to degrade IKZF1, IKZF3 and CK1 alpha.
No product in this corpus aims at Cereblon (CRBN) yet. Drugs bind the molecule precisely: to switch it off, flag the cell for the immune system, or deliver a payload.
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.)
Sources: Human Protein Atlas CRBN tissue; Open Targets ENSG00000113851 associations
First described 2000. 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". Source.
Substrate receptor of the CRL4 (CUL4, DDB1, RBX1) E3 ubiquitin ligase; immunomodulatory drugs redirect it to degrade IKZF1, IKZF3 and CK1 alpha.
RNA: low tissue specificity, detected in all normal tissues.
Medium: Adipose tissue, Bone marrow, Breast, Caudate, Cervix, Endometrium, Epididymis, Esophagus.
Medium only: carcinoid, cervical cancer, colorectal cancer, endometrial cancer.
HPA CRBN tissue · HPA CRBN pathology · HPA protein class: FDA approved drug targets
Human Protein Atlas version 25.1, antibody staining at reliability approved, enhanced or supported; used under CC BY-SA 3.0. Staining counts are patients per level in the atlas cohort, not population prevalence.
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Multiple myeloma | nearly all% | Cereblon expression at diagnosis; required for lenalidomide and pomalidomide activity, lost in a minority of refractory disease | doi.org |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
Query for this target: (TITLE:"Cereblon" OR ABSTRACT:"Cereblon" OR TITLE:"CRBN" OR ABSTRACT:"CRBN") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Cereblon (CRBN), not a curated reading list.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Pomalidomide, Newly diagnosed multiple myeloma, transplant-eligible, Lenalidomide.
Shares IKZF1 (Ikaros), IKZF3 (Aiolos), Cereblon E3 ligase modulators (CELMoDs), Lenalidomide.
Shares Cereblon E3 ligase modulators (CELMoDs), Newly diagnosed multiple myeloma, transplant-eligible, Lenalidomide, Multiple myeloma.
Shares Cereblon E3 ligase modulators (CELMoDs), Pomalidomide, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Newly diagnosed multiple myeloma, transplant-eligible, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Newly diagnosed multiple myeloma, transplant-eligible, Multiple myeloma.
Shares Newly diagnosed multiple myeloma, transplant-ineligible, Newly diagnosed multiple myeloma, transplant-eligible, Relapsed or refractory multiple myeloma, Multiple myeloma.
Shares Newly diagnosed multiple myeloma, transplant-eligible, Lenalidomide, Multiple myeloma.