Thalidomide-4-O-CH2-COO(t-Bu)

Background Introduction

Thalidomide-4-O-CH2-COO(t-Bu) is a thalidomide-derived ligand engineered with a tert-butyl-protected carboxymethyl linker at the 4-hydroxy position of the parent scaffold. Thalidomide and its analogs have established themselves as privileged E3 ligase recruiters in targeted protein degradation, playing a pivotal role in the development of PROTACs (Proteolysis Targeting Chimeras) and molecular glues. The tert-butyl protection enhances chemical stability and provides a ready-to-deprotect handle for further conjugation, making this building block highly valuable for next-generation therapeutic design.

Mechanism

Thalidomide-4-O-CH2-COO(t-Bu) functions as a Cereblon (CRBN) E3 ligase ligand, binding specifically to the CRBN component of the CUL4-CRBN E3 ubiquitin ligase complex. Once conjugated to a ligand with affinity for a protein of interest, this PROTAC reagent brings the target protein into close proximity with CRBN, facilitating ubiquitination and subsequent proteasomal degradation. The installed tert-butyl-protected carboxylic acid facilitates synthetic modification, ensuring efficient linker installation and maintaining ligand stability during multistep PROTAC assembly.

Applications

Thalidomide-4-O-CH2-COO(t-Bu) is widely used in chemical biology, medicinal chemistry, and drug discovery for constructing CRBN-based PROTACs and molecular glue therapeutics. Its robust structure and modular linker allow rapid customization of bifunctional molecules. Key applications include:

• Synthesis of CRBN-recruiting PROTACs for research and preclinical studies
• Development of custom molecular glues for selective protein degradation
• Structure-activity relationship (SAR) and medicinal chemistry optimization of degraders
• Academic and pharmaceutical research requiring high-purity E3 ligase ligands for targeted protein degradation technology

• 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
• tert-Butyl protected carboxyl group enhances chemical stability during synthesis and storage.
• Optimized for efficient CRBN E3 ligase recruitment in targeted protein degradation PROTAC applications.