2022年12月19日 · 研究表明，IMiDs主要通过结合CRL4 E3泛素连接酶 (CRL4CRBN) 复合物的底物受体蛋白Cereblon (CRBN) 发挥其抗骨髓瘤活性。 通过结合CRBN，IMiDs改变了其底物的特性，导致骨髓瘤细胞存活所必需的蛋白质的泛素化和蛋白酶体降解。

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. Despite this...

2016年6月22日 · Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4 CRBN E3 ubiquitin ligase. Here we report the identification of a new cereblon...

最新的AACR会议上，已经有一批公司使用新型CRBN配体，包括 Arvinas公司 的第二代AR降解剂ARV-766， C4公司 的BRD9 降解剂CFT8634和BRAF V600E降解剂CFT1946，以及Kymera的IRAK4降解剂KT474（图7）。 图7. 基于新型CRBN配体的PROTAC. CC-122（avadomide）也具有抗癌和免疫调节活性。 有两个课题组分别采用了CC-122的类似物用于PROTACs的设计中，如图8所示，Nurix公司在他们的专利中（WO 2021113557）发表了一类BTX降解剂，另外也有一 …

Cereblon (CRBN), a target of IMiDs, forms the CRL4 E3 ubiquitin ligase complex (CRL4 CRBN) with DDB1, CUL4A and RBX1. The insight into the molecular mechanism of IMiDs action has advanced dramatically since the identification of cereblon (CRBN) as their direct target.

2016年2月24日 · Thalidomide and its derivative lenalidomide bind the CRL4CRBN E3 ubiquitin ligase and target protein substrates for degradation; structural and functional data determined here show that casein ...

2022年9月16日 · It is now known that IMiDs exert their anti-myeloma activity mainly by binding cereblon (CRBN), the substrate receptor protein of the CRL4 E3 ubiquitin ligase (CRL4 CRBN) complex. By binding CRBN, IMiDs alter its substrate specificity, leading to ubiquitination and proteasomal degradation of proteins essential for MM cell survival.

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. Despite this clinical significance, the physiological regulation of CRBN remains largely unknown.

2016年7月14日 · Immunomodulatory drugs bind to cereblon (CRBN) to confer differentiated substrate specificity on the CRL4 (CRBN) E3 ubiquitin ligase. Here we report the identification of a new cereblon modulator, CC-885, with potent anti-tumour activity.

2017年3月30日 · Synthesis of novel glutarimide ligands for the E3 ligase substrate receptor Cereblon (CRBN): Investigation of their binding mode and antiproliferative effects against myeloma cell lines.