Thalidomide-O-amido-PEG3-C2-NH2 hydrochloride

Background Introduction

Thalidomide-O-amido-PEG3-C2-NH2 hydrochloride is a high-purity small molecule designed as an E3 ligase ligand-linker conjugate. It incorporates thalidomide, a well-established cereblon (CRBN) E3 ubiquitin ligase ligand, covalently connected to a polyethylene glycol (PEG3) linker and an alkyl amine terminal group. This structure is highly suitable for the design and synthesis of proteolysis targeting chimeras (PROTACs) and other targeted protein degradation molecules.

Mechanism

This molecule functions by recruiting the CRBN E3 ubiquitin ligase complex through the thalidomide moiety. The PEG3 linker ensures optimized spatial orientation and flexibility, facilitating the connection of this E3 ligase ligand to a target protein binder via its terminal amine group. In PROTAC applications, the conjugate brings the E3 ligase into close proximity with the target protein, enabling ubiquitination and subsequent proteasomal degradation of the target.

Applications

Thalidomide-O-amido-PEG3-C2-NH2 hydrochloride is widely used in the development of PROTACs and molecular glues for targeted protein degradation research. It serves as a modular building block, enabling medicinal chemists to link diverse target-binding ligands to the CRBN E3 ligase. This compound streamlines the process of synthesizing custom PROTAC molecules for the discovery of novel therapeutics in oncology, neurodegenerative diseases, and other fields relying on targeted protein modulation.