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Target intelligence / Profile preview
Cereblon-containing CRL4^CRBN E3 ubiquitin ligase complex (CRL4^CRBN)
- Target
- CRL4^CRBN
- Molecular classification
- E3 ubiquitin ligase complex, Cereblon complex
01
Overview
The cereblon-containing CRL4^CRBN E3 ubiquitin ligase complex is a key target of immunomodulatory drugs (IMiDs) like lenalidomide. Lenalidomide binding to cereblon alters the complex's substrate specificity, leading to the degradation of specific transcription factors (IKZF1, IKZF3) and other proteins (CK1α), resulting in downstream anti-cancer and immunomodulatory effects. It plays a critical role in multiple myeloma, myelodysplastic syndromes, and B-cell lymphomas.
- Other names
- CereblonCRBNCRL4
02
Mechanism of action
Lenalidomide binds to cereblon, altering the substrate specificity of the CRL4^CRBN E3 ubiquitin ligase, leading to recruitment and proteasomal degradation of IKZF1, IKZF3, and CK1α.
03
Biological functions
Protein ubiquitinationProtein degradationTranscription factor regulationImmune regulationCell cycle regulation
04
Disease associations
Multiple myelomaMyelodysplastic syndromesB-cell lymphomasCancer
05
Safety considerations
TeratogenicityThrombosisCytopenias
06
Interacting drugs
Lenalidomide
07
Biomarkers
IKZF1 expressionIKZF3 expressionCK1α expressiondel(5q) chromosomal deletion
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