2021年9月6日 · Binding of IMiDs to Cereblon (CRBN), the substrate receptor of the CRL4 CRBN E3 ubiquitin ligase, induces cancer cell death by targeting key neo-substrates for degradation....

Cereblon is a protein that in humans is encoded by the CRBN gene. [5] The gene that encodes the cereblon protein is found on the human chromosome 3 , on the short arm at position p26.3 from base pair 3,190,676 to base pair 3,221,394.

CRBN, a 442-amino acid protein with multifunction, locates in the cytoplasm, nucleus, and peripheral membrane of the human brain and other tissues . The diverse roles of CRBN on cell metabolism and disease genesis have been extensively studied.

2021年9月22日 · Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin complex. The binding target of CRBN varies according to tissues and cells, and the protein regulates various biological functions by regulating tissue-specific targets.

Cereblon (CRBN) is a substrate recognition protein in the E3-ligase ubiquitin complex. The binding target of CRBN varies according to tissues and cells, and the protein regulates various biological functions by regulating tissue-specific targets. As new endogenous targets of CRBN have been identifie …

2018年11月13日 · To overcome this difficulty, we generated humanized cereblon (CRBN I391V) mice thereby providing an animal model to unravel complex mechanisms of action in a murine physiological setup. In our current study, we investigated the degradative effect toward IKZF1 and CK-1α, a target substrate of IMiDs.

2014年8月10日 · Here we present the crystal structure of human CRBN bound to DDB1 and the drug lenalidomide. A hydrophobic pocket in the thalidomide-binding domain (TBD) of CRBN accommodates the glutarimide...

2025年2月20日 · To tackle this, we engineer an intermediate human CRBN construct (CRBN_ΔHBD), that contains all important structural regions for compound binding, and purify from a simple, convenient E. coli expression system. We develop several binary and ternary interaction assays and show highly desirable properties of CRBN_ΔHBD for the evaluation of ...

2024年11月16日 · Many of these lines express human cereblon (CRBN), making them particularly valuable for research on immunomodulatory drugs (IMiDs) and their mechanisms of action. There are 4 new genetically engineered models based on germinal center activation of NFkB together with Nsd2, Ccnd1, Myc or Bcl2 .

The majority of clinical degraders utilize an immunomodulatory imide drug (IMiD)-based derivative that directs their target to the E3 ligase receptor cereblon (CRBN); however, identification of IMiD molecular glue substrates has remained underexplored. To tackle this, …