Thalidomide-4-NH-PEG1-COO(t-Bu)

Background Introduction

Thalidomide-4-NH-PEG1-COO(t-Bu) is a specialized thalidomide derivative utilized in the design of targeted protein degraders such as PROTACs. Incorporating a short polyethylene glycol (PEG1) unit and a tert-butyl protected carboxyl group at the 4-amino position, this compound offers improved solubility, customizable linker length, and convenient conjugation chemistry. Thalidomide-based molecules serve as essential recruiters of the Cereblon (CRBN) E3 ubiquitin ligase, a cornerstone technology in targeted protein degradation therapeutics and research.

Mechanism

Thalidomide-4-NH-PEG1-COO(t-Bu) functions by specifically binding to the CRBN component of the CUL4-CRBN E3 ubiquitin ligase complex. In PROTAC architecture, the thalidomide moiety acts as an E3 ligase ligand, while the PEG1 linker provides spatial flexibility and improved pharmacokinetic properties. Upon joining an appropriate target protein ligand, this bifunctional modulator enables the proximity-induced ubiquitination and subsequent proteasomal degradation of the protein of interest. The tert-butyl protected carboxylic acid ensures chemical stability during complex synthetic steps and allows efficient deprotection for downstream conjugation.

Applications

Thalidomide-4-NH-PEG1-COO(t-Bu) is widely applied in the synthesis of CRBN-recruiting PROTACs and other molecular glues aimed at selective protein degradation. The PEG1 linker enhances aqueous compatibility and modulates intracellular distribution, making this compound ideal for medicinal chemistry optimization. Main application areas include:

• Development of CRBN-based targeted degraders for drug discovery
• Assembly of molecular glues for protein knockdown studies
• Linker optimization and structure-activity relationship (SAR) exploration
• Preparation of PROTAC libraries for biological screening
• Custom synthesis projects in academic labs and contract research organizations

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• PEG1 linker enhances solubility and cell permeability for improved PROTAC performance
• tert-Butyl protected carboxyl group ensures efficient conjugation and easy deprotection for versatile synthesis