Thalidomide-O-amido-PEG-C2-NH2 hydrochloride

Background Introduction

Thalidomide-O-amido-PEG-C2-NH2 hydrochloride is a specialized E3 ligase ligand-linker conjugate commonly utilized in the field of targeted protein degradation. This product features a thalidomide moiety, which acts as a cereblon (CRBN) E3 ligase ligand, chemically attached via a hydrophilic polyethylene glycol (PEG) linker. Designed for use in the development of PROTACs (Proteolysis Targeting Chimeras), it enables researchers to engineer bifunctional molecules for innovative protein degradation strategies.

Mechanism

The mechanism of Thalidomide-O-amido-PEG-C2-NH2 hydrochloride centers on its ability to recruit the CRBN E3 ubiquitin ligase. In PROTAC design, this ligand-linker conjugate is coupled to a target protein ligand via its terminal amine (NH2) group, forming a bifunctional molecule. Upon binding to both the E3 ligase and the target protein, the PROTAC induces proximity-driven ubiquitination of the target, leading to its recognition and degradation by the proteasome. The PEG linker provides flexibility, optimizes spatial arrangement, and improves cellular permeability and solubility.

Applications

Thalidomide-O-amido-PEG-C2-NH2 hydrochloride is widely applied in the synthesis of PROTAC molecules for chemical biology and drug discovery research. By linking it to ligands that bind disease-associated proteins, researchers can selectively degrade otherwise undruggable proteins implicated in cancer, neurodegeneration, and autoimmune disorders. This conjugate is crucial for rapid prototyping and optimization of PROTACs in preclinical studies, offering a reliable means to harness targeted protein degradation for therapeutic innovation.