Molecular Classification
E3 ubiquitin ligase component, Substrate receptor
Other Names
MRT2, MRT2A, Cereblon
Disease Roles
Intellectual disabilityCancerHematological malignancies

Cereblon Overview

Cereblon (CRBN) is a protein that serves as a substrate receptor for the Cullin-RING E3 ubiquitin ligase complex (CRL4^CRBN), which targets specific proteins for ubiquitination and subsequent degradation. It plays a role in developmental processes, ion channel regulation, and is a key target for immunomodulatory drugs like thalidomide and its analogs. CRBN is also exploited in PROTAC technology to selectively degrade disease-relevant proteins.

Mechanism of Action

Thalidomide and its analogs bind to cereblon, acting as "molecular glue degraders" to promote interaction between cereblon and neosubstrates, leading to their ubiquitination and proteasomal degradation.

Biological Functions

Ubiquitination
Proteasomal degradation
Regulation of fibroblast growth factors
Ion channel regulation
Limb outgrowth during embryonic development
Presynaptic glutamate release

Disease Associations

Intellectual disability
Cancer
Hematological malignancies

Safety Considerations

  • Teratogenicity (Thalidomide exposure during pregnancy)
  • Potential for off-target effects with PROTACs

Interacting Drugs

Thalidomide
Lenalidomide
Pomalidomide