Technical Articles

This article systematically elaborates on the molecular characteristics and biological functions of the CRBN/DDB1 complex protein, describing the structural localization of CRBN as the substrate recognition component of the CUL4-RBX1-DDB1-CRBN E3 ubiquitin ligase complex and its interaction mode with the DDB1 adaptor protein, analyzing the molecular mechanism by which the CRBN C-terminal aromatic cage forms the immunomodulatory drug binding pocket and mediates the recruitment of endogenous and neo-substrates, and discussing the core platform value of this complex in the design of PROTACs and molecular glue degraders as well as the advantages of CRBN-based degraders in the chemical space of oral absorption.

This article systematically elucidates the molecular basis of CRBN and DDB1 forming a functional complex, analyzes its core role as the substrate recognition module of the CUL4-RING E3 ubiquitin ligase complex, and explores the pivotal position of this complex in the development of PROTACs and molecular glue drugs.