Thalidomide-O-amido-C6-NH2 hydrochloride

Background Introduction

Thalidomide-O-amido-C6-NH2 hydrochloride is a premium E3 ligase ligand-linker conjugate designed for use in targeted protein degradation technology, most notably in PROTAC (Proteolysis Targeting Chimera) research and development. This compound combines a thalidomide-based cereblon (CRBN) ligand with a hexyl (C6) amide linker terminated with an amine group, offering high versatility for the synthesis of bifunctional molecules. With its optimized structure, Thalidomide-O-amido-C6-NH2 hydrochloride enables researchers to efficiently generate PROTACs for preclinical and drug discovery applications.

Mechanism

Thalidomide-O-amido-C6-NH2 hydrochloride functions as a modular building block in PROTAC synthesis. The thalidomide moiety serves as a high-affinity ligand for the E3 ubiquitin ligase cereblon (CRBN), a key component responsible for tagging target proteins with ubiquitin for proteasomal degradation. The C6 amido linker provides flexible spatial orientation, while the terminal amine allows for straightforward conjugation via amide coupling or other bioconjugation strategies to a wide array of protein-targeting ligands. When fashioned into a PROTAC, this conjugate bridges the E3 ligase and the target protein, resulting in selective ubiquitination and degradation of the target protein within the cell.

Applications

Thalidomide-O-amido-C6-NH2 hydrochloride is widely used in the design and synthesis of PROTACs, molecular glues, and other heterobifunctional molecules. Its optimized structure enhances the development of chemical probes for protein function study and accelerates the discovery of novel therapeutics by enabling targeted protein degradation. This compound is particularly valuable in oncology, neurodegenerative disease, and immunology research, where precise protein knockdown is critical for understanding disease mechanisms and discovering next-generation therapeutics. Compatible with standard solid- and solution-phase synthetic techniques, it supports efficient library generation and rapid lead optimization in drug discovery programs.