Thalidomide-5-NH-CH2-COO(t-Bu)

Background Introduction

Thalidomide-5-NH-CH2-COO(t-Bu) is a strategically engineered derivative of thalidomide, one of the most widely used Cereblon (CRBN) E3 ligase ligands in targeted protein degradation research. By introducing a carbamate linker at the 5-amino position appended with a tert-butyl protected carboxyl group, this molecule exhibits enhanced chemical stability and versatility for the synthesis of PROTACs (Proteolysis Targeting Chimeras) and other heterobifunctional degraders. Its unique structure ensures optimal positioning of the functionalized linker to aid in efficient conjugation during degrader development.

Mechanism

Thalidomide-5-NH-CH2-COO(t-Bu) operates as a high-affinity ligand for the CRBN protein, the substrate receptor subunit in the CUL4A-CRBN E3 ubiquitin ligase complex. When incorporated into PROTACs, this compound recruits the CRBN E3 ligase to the target protein by virtue of its selective binding. The tert-butyl ester serves as a protected acidic handle, facilitating straightforward linker modification and conjugation. Upon binding, the proximity-induced ubiquitination of the target protein is initiated, ultimately leading to its recognition and degradation by the 26S proteasome system.

Applications

Thalidomide-5-NH-CH2-COO(t-Bu) is an invaluable building block in the design of CRBN-recruiting PROTACs and molecular glue degraders for targeted protein degradation. Its stable and modifiable linker enables seamless conjugation with a broad spectrum of protein-targeting ligands, supporting advanced SAR studies and rational PROTAC optimization.

Common applications include:

• Synthesis of CRBN-based PROTAC molecules for degrader screening and development
• Generation of novel molecular glues for modulating protein-protein interactions
• Medicinal chemistry, probe design, and preclinical drug discovery investigations
• Custom PROTAC or degrader library generation by CROs and academic labs focused on targeted protein degradation research

• 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
• Enhanced site-selectivity at the 5-amino position allows for diversified PROTAC molecule design.
• tert-Butyl ester protection guarantees compatibility with various coupling chemistries, streamlining synthesis workflows.