Thalidomide-linker 1

Background Introduction

Thalidomide-linker 1 is a specially designed bifunctional molecule based on thalidomide, serving as an E3 ligase ligand integrated with a chemical linker. Thalidomide derivatives are widely used as recruiting elements to harness the activity of the cereblon (CRBN) E3 ubiquitin ligase complex, a crucial component in targeted protein degradation technologies such as PROTACs (Proteolysis Targeting Chimeras). This product bridges the ability to hijack the body’s natural ubiquitin-proteasome system for selective degradation of target proteins.

Mechanism

Thalidomide-linker 1 operates as an E3 ligase ligand-linker conjugate by exploiting the high-affinity interaction between its thalidomide moiety and the cereblon (CRBN) component of the CRL4 E3 ubiquitin ligase complex. The linker provides the flexibility required to conjugate thalidomide to various warheads or target protein ligands, thus forming bifunctional molecules like PROTACs. Upon proper assembly, these chimeric molecules bring the target protein into proximity with the E3 ligase, enabling ubiquitination and subsequent proteasomal degradation of the target.

Applications

Thalidomide-linker 1 is widely utilized in the design and synthesis of PROTACs and other targeted protein degradation compounds. It is ideal for researchers developing novel therapeutics to selectively degrade disease-relevant proteins, particularly in oncology, immunology, and neurodegenerative disorders. Thalidomide-linker 1 enables the modular construction of bifunctional molecules for preclinical drug discovery, helping accelerate advances in chemical biology and targeted therapeutics.