Thalidomide-NH-PEG1-NH2 hydrochloride

Background Introduction

Thalidomide-NH-PEG1-NH2 hydrochloride is a versatile E3 ligase ligand-linker conjugate widely employed in the field of targeted protein degradation, particularly in PROTAC technology. It combines a thalidomide-based moiety, which binds to the cereblon (CRBN) E3 ubiquitin ligase, with a short, hydrophilic PEG1 linker and terminal amine functionality. This structure enables researchers and medicinal chemists to construct custom PROTAC molecules for probing and drug discovery applications.

Mechanism

Thalidomide-NH-PEG1-NH2 hydrochloride operates by exploiting the ubiquitin-proteasome system. The thalidomide portion selectively binds to the CRBN E3 ligase, one of the key components in the E3 ubiquitin ligase complex. The PEG1 linker provides hydrophilicity and optimal spatial arrangement, while the terminal amine allows for easy conjugation with various ligands targeting proteins of interest. When incorporated into a PROTAC, this conjugate brings the E3 ligase and target protein into proximity, leading to ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

This product is ideal for the efficient design and synthesis of PROTACs and molecular glues. Thalidomide-NH-PEG1-NH2 hydrochloride is widely used in early-stage drug development, target validation, and functional genomics studies. Researchers utilize it to create customized PROTACs that induce selective degradation of disease-relevant proteins, facilitating novel therapeutic approaches for oncology, immunology, neurodegenerative diseases, and beyond. Its high purity and robust performance make it a preferred building block for academic and pharmaceutical research in targeted protein degradation.