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

Background Introduction

Thalidomide-5-O-CH₂-COO(t-Bu) is a structural analog of thalidomide, a cornerstone molecule in the development of immunomodulatory imide drugs (IMiDs) and CRBN-based E3 ligase ligands for targeted protein degradation technologies. This derivative features a tert-butyl-protected carboxyl linker specifically attached at the 5-hydroxy position, offering valuable chemical modification sites for further conjugation. Its design enhances both chemical stability and the flexibility needed during PROTAC synthesis and related applications.

Mechanism

Thalidomide-5-O-CH₂-COO(t-Bu) serves as a potent ligand for the Cereblon (CRBN) E3 ubiquitin ligase. By binding to CRBN, it facilitates the recruitment of the CUL4-CRBN E3 ubiquitin ligase complex, triggering the ubiquitination and subsequent degradation of target proteins when tethered to a suitable target protein ligand via a linker. The tert-butyl-protected carboxyl group at the 5-position offers an effective and stable attachment point, enabling controlled PROTAC assembly and providing synthetic versatility without compromising ligand affinity for CRBN.

Applications

Thalidomide-5-O-CH₂-COO(t-Bu) is an essential chemical building block for the design and synthesis of CRBN-based PROTACs and other targeted degraders. Its unique 5-hydroxy substitution and protected linker tail make it valuable for a wide array of research and development applications, including:

• Creation of bifunctional molecules for targeted protein degradation in PROTAC discovery
• Synthesis of molecular glues that modulate CRBN-mediated ubiquitination pathways
• Medicinal chemistry campaigns and SAR (structure-activity relationship) studies for degrader optimization
• Custom syntheses for use in CRO services and academic research targeting novel protein targets

This compound supports the rapid advancement of TPD technology, aiding in both drug discovery and fundamental biological 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
• Highly selective 5-position modification optimizes binding affinity for targeted protein degradation.
• tert-Butyl protected carboxyl group enhances synthetic flexibility for efficient CRBN E3 ligase PROTAC assembly.