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

Background Introduction

Thalidomide-NH-CH2-COO(t-Bu) is a synthetic derivative of thalidomide engineered for use as a Cereblon (CRBN) E3 ligase ligand in the design and synthesis of PROTACs (Proteolysis Targeting Chimeras). By appending a tert-butyl protected carboxyl linker via an amide bond, this reagent offers improved synthetic versatility and stability, making it a popular building block for developing targeted protein degraders in chemical biology and drug discovery applications.

Mechanism

Thalidomide-NH-CH2-COO(t-Bu) acts by binding to the CRBN component of the CUL4-CRBN E3 ubiquitin ligase complex. When incorporated into a PROTAC molecule, this CRBN ligand recruits the E3 ligase to the proximity of the target protein, enabled by a bifunctional linker. This induced proximity leads to ubiquitination and subsequent proteasomal degradation of the target protein. The tert-butyl protected carboxyl functionality ensures chemical integrity during multi-step synthesis and can be selectively deprotected for further functionalization, allowing flexible incorporation into different PROTAC architectures.

Applications

Thalidomide-NH-CH2-COO(t-Bu) is broadly utilized in the development and optimization of CRBN-based PROTACs, offering a robust intermediate for conjugation to various target ligands. Key applications include:

• Design of novel CRBN-recruiting degrader molecules for targeted protein degradation
• Structure-activity relationship (SAR) studies for medicinal chemistry optimization
• Development of molecular glues for selective CRBN-mediated degradation pathways
• Construction of custom bifunctional molecules for academic research and CRO synthesis
• Exploration of alternative linker strategies to tune PROTAC efficiency and pharmacokinetic profiles

• 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 chemical stability due to tert-butyl protected linker, facilitating efficient downstream conjugation in synthesis workflows.
• Optimized for cereblon (CRBN)-based PROTAC design, enabling targeted protein degradation applications.