Thalidomide-O-C8-COOH

Background Introduction

Thalidomide-O-C8-COOH is a derivative of thalidomide, one of the most established E3 ligase ligands used in PROTAC (Proteolysis Targeting Chimera) technology. It features an extended octyl (C8) aliphatic linker attached via an ether bond to the thalidomide core and terminates in a carboxylic acid group. This design facilitates versatile conjugation strategies for synthesizing advanced PROTACs and molecular glues targeting the CRBN (Cereblon) E3 ubiquitin ligase complex. The increased linker length offered by the C8 chain provides added spatial flexibility, improving the range of target engagement in heterobifunctional degrader synthesis.

Mechanism

Thalidomide-O-C8-COOH functions as a high-affinity ligand for the CRBN component of the CUL4-CRBN E3 ubiquitin ligase complex. Upon incorporation into a PROTAC molecule, the thalidomide motif binds selectively to CRBN, effectively recruiting the E3 ligase machinery. The carboxyl-terminated C8 linker allows for convenient conjugation to a wide array of target protein ligands, facilitating proximity-induced ubiquitination and the subsequent proteasomal degradation of disease-relevant proteins. The extended linker improves flexibility, enabling optimized spatial orientation and potentially enhancing the efficiency of ternary complex formation and target degradation.

Applications

Thalidomide-O-C8-COOH is widely used in the design and synthesis of CRBN-recruiting PROTACs and molecular glue degraders. Its robust chemical structure enables convenient ligation with various binding moieties, supporting medicinal chemistry campaigns aimed at discovering and optimizing next-generation protein degraders. Key applications include:

• Development of custom CRBN-based PROTAC libraries for high-throughput screening and SAR studies
• Synthesis of bifunctional molecules for targeted protein degradation in oncology, neuroscience, and immunology research
• Design of novel molecular glues for selective CRBN engagement
• Scaffold for advanced degrader construction in academic and industrial drug discovery pipelines

• 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
• Optimal for constructing CRBN-recruiting PROTACs, enhancing targeted protein degradation efficiency.
• Features a flexible C8 linker, providing improved solubility and optimal spatial arrangement for bioconjugation in drug discovery applications.