Thalidomide-NH-CH2-COOH

Background Introduction

Thalidomide-NH-CH2-COOH is a thalidomide derivative specifically engineered for use in targeted protein degradation research. As a potent immunomodulatory imide drug (IMiD) analog, it acts as an efficient Cereblon (CRBN) E3 ligase ligand and is an integral component in Proteolysis Targeting Chimera (PROTAC) technologies. With the introduction of an amino-methylene-carboxyl linker at the 4-position, Thalidomide-NH-CH2-COOH provides a reactive and flexible carboxyl functionality for seamless conjugation and PROTAC construction, supporting advanced degrader design in drug discovery.

Mechanism

Thalidomide-NH-CH2-COOH operates by binding to the Cereblon (CRBN) subunit of the CUL4-CRBN E3 ubiquitin ligase complex. By serving as a high-affinity E3 ligase ligand, it enables the recruitment of CRBN to PROTAC molecules. When conjugated to a ligand for a protein of interest via its carboxyl-functionalized linker, it brings the E3 ligase in close proximity to the target protein, facilitating ubiquitination and subsequent proteasomal degradation. The NH-CH2-COOH linker ensures efficient and site-specific conjugation, supporting optimized PROTAC design and target engagement.

Applications

Thalidomide-NH-CH2-COOH is highly valued in the synthesis and optimization of CRBN-based PROTACs and molecular glue degraders. Its reactive carboxylic acid linker is ideal for coupling with diverse target protein ligands, enabling rapid development of bifunctional molecules for research and drug development. Key applications include:

• Construction of CRBN E3 ligase-recruiting segments in PROTAC synthesis
• Medicinal chemistry projects focused on target validation and SAR studies
• Accelerated development of molecular glues for selective protein degradation
• Custom synthesis and library generation for pharmaceutical R&D and academic 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
• Versatile amine-carboxyl functionalization enables easy conjugation to bioactive molecules.
• Highly effective for designing CRBN E3 ligase-recruiting PROTACs, facilitating targeted protein degradation applications.