Thalidomide-4-NH-PEG2-COO(t-Bu)

Background Introduction

Thalidomide derivatives have emerged as cornerstone ligands for recruiting the Cereblon (CRBN) E3 ubiquitin ligase complex in the rapidly expanding field of targeted protein degradation. Thalidomide-4-NH-PEG2-COO(t-Bu) is a strategically designed thalidomide analog featuring a PEG2 (ethylene glycol) linker at the 4-amino position with a tert-butyl-protected carboxyl group. This structure provides superior water solubility and flexible chemical reactivity, enabling scientists to efficiently build next-generation PROTACs and molecular glue degraders for research and therapeutic applications.

Mechanism

Thalidomide-4-NH-PEG2-COO(t-Bu) functions by specifically binding to the CRBN substrate receptor within the CUL4A-CRBN E3 ubiquitin ligase complex. Through this high-affinity interaction, it serves as a recruitment handle for CRBN upon conjugation to a ligand for the protein of interest, enabling the targeted ubiquitination and proteasomal degradation of disease-related proteins. The PEG2 spacer improves linker flexibility and membrane permeability, while the tert-butyl-protected carboxyl group allows for facile, orthogonal conjugation during PROTAC assembly.

Applications

Thalidomide-4-NH-PEG2-COO(t-Bu) is an ideal building block for the synthesis of CRBN-based PROTACs, molecular glues, and other targeted protein degradation tools. Its enhanced solubility and functional versatility make it highly valuable for drug discovery, hit-to-lead development, and protein function studies in both academic and pharmaceutical research settings. Main applications include:

• Construction of CRBN E3 ligase ligand modules for PROTAC synthesis
• Development of modular protein degraders with improved drug-like properties
• Structure-activity relationship (SAR) optimization in degrader design
• Chemical biology and target identification studies
• Custom synthesis for medicinal chemistry and early-stage drug development

• 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
• Polyethylene glycol (PEG2) linker enhances aqueous solubility and biocompatibility.
• Perfect for constructing CRBN-recruiting PROTACs with customizable conjugation flexibility.