Thalidomide-NH-(CH2)2-NH2 TFA

Background Introduction

Thalidomide-NH-(CH2)2-NH2 TFA is a functionalized thalidomide derivative designed for use as a Cereblon (CRBN) E3 ligase ligand in targeted protein degradation strategies such as PROTACs. This molecule features a primary amine-terminated ethylene linker attached to the thalidomide core via a stable amide bond, with the TFA (trifluoroacetic acid) salt form ensuring improved solubility and handling. Innovations in ligand design like this compound have enabled more effective conjugation and higher versatility in constructing degraders for chemical biology and drug discovery applications.

Mechanism

Thalidomide-NH-(CH2)2-NH2 TFA binds specifically to the Cereblon (CRBN) component of the CUL4-CRBN E3 ubiquitin ligase complex, serving as the E3 ligase-recruiting element in bifunctional molecules. The ethylene diamine linker with a terminal primary amine offers a convenient site for chemical conjugation to a target protein ligand via standard coupling reactions. Once incorporated into a PROTAC, the molecule bridges CRBN and the target protein, leading to targeted ubiquitination and proteasomal degradation of the protein of interest.

Applications

Thalidomide-NH-(CH2)2-NH2 TFA is extensively employed as a key building block for the synthesis of CRBN-based PROTACs and molecular glue degraders. Its amine-terminated linker allows facile functionalization, enabling rapid generation of diverse degrader libraries for structure-activity relationship (SAR) studies and hit-to-lead optimization. Typical applications include:

• Development of custom CRBN-recruiting PROTACs for drug discovery and target validation
• Synthesis of CRBN-based molecular glues for selective protein degradation studies
• Rapid assembly of PROTAC conjugates via amide or urea bond formation
• Use in medicinal chemistry, hit expansion, and CRO/academic research settings

• 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
• Amino-functionalized linker allows versatile conjugation to a wide variety of target ligands, enhancing PROTAC design flexibility.
• Optimized for efficient recruitment of the CRBN E3 ligase, enabling potent targeted protein degradation in research and drug discovery.