Thalidomide-4-NH-PEG1-NH2 TFA

Background Introduction

Thalidomide-4-NH-PEG1-NH2 TFA is a functionalized derivative of thalidomide that has been modified at the 4-amino position with a monodisperse polyethylene glycol (PEG1) chain terminating in a primary amine. The presence of the TFA (trifluoroacetic acid) salt form ensures enhanced solubility and stability for synthetic applications. As a CRBN (Cereblon) E3 ligase ligand, this compound is a valuable building block for the development of PROTACs (Proteolysis Targeting Chimeras), enabling targeted protein degradation.

Mechanism

Thalidomide-4-NH-PEG1-NH2 TFA binds specifically to the CRBN (Cereblon) substrate receptor of the CRL4^CRBN E3 ubiquitin ligase complex. This ligand enables the recruitment of CRBN to PROTAC molecules. The PEG1 linker offers improved solubility and spatial flexibility, while the terminal primary amine allows straightforward coupling to a variety of target protein ligands. By bridging CRBN and the target protein ligand, it facilitates proximity-dependent ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

Thalidomide-4-NH-PEG1-NH2 TFA is widely used for the synthesis of CRBN-recruiting PROTACs and related heterobifunctional degraders. Its unique PEG1 linker improves overall pharmacokinetic properties, cell permeability, and water solubility of chimeric molecules. This compound is ideal for:

• Construction of CRBN-based protein degrader libraries
• Development of customized PROTACs for drug discovery and target validation
• Structure-activity relationship (SAR) studies investigating linker effects in PROTAC design
• Medicinal chemistry research and custom synthesis in CRO/academic labs seeking to expand their targeted protein degradation toolkits.

• 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
• Featuring a PEG1 linker, this ligand enhances solubility and cell permeability in PROTAC design.
• Amino-terminated structure allows flexible conjugation with diverse warheads for efficient CRBN E3 ligase recruitment.