Thalidomide-NH-(CH2)2-NH-Boc

Background Introduction

Thalidomide-NH-(CH2)2-NH-Boc is a functionalized thalidomide derivative designed for use as an E3 ligase ligand in targeted protein degradation platforms, such as PROTACs (Proteolysis Targeting Chimeras). The compound incorporates a thalidomide core—the well-characterized CRBN E3 ligase binder—linked via a flexible ethylene diamine (NH-(CH2)2-NH-) spacer to a Boc-protected amine, thereby yielding an ideal handle for further conjugation and PROTAC design.

Mechanism

This molecule operates by binding to the immunomodulatory protein Cereblon (CRBN), the substrate recognition subunit of the CUL4A-CRBN E3 ubiquitin ligase complex. The thalidomide moiety enables high-affinity interaction with CRBN, bringing the E3 ligase in proximity to a target protein when coupled with a suitable ligand. The ethylene diamine linker offers flexibility, and the terminal Boc-protected amine facilitates controlled deprotection and functionalization, allowing efficient coupling of diverse target protein ligands to engineer bifunctional degraders. The recruited ligase catalyzes the polyubiquitination and proteasomal degradation of the tagged target protein.

Applications

Thalidomide-NH-(CH2)2-NH-Boc serves as a foundational building block for the synthesis of CRBN-recruiting PROTACs and related molecular glue degraders. Principal applications include:

• Development of structure-activity relationship (SAR) libraries by enabling modular attachment of varied protein-binding warheads.
• Synthesis of custom degraders for drug discovery and target validation efforts.
• Use in medicinal chemistry campaigns to optimize linker length, flexibility, and degradation efficiency.
• Academic and CRO research to expand the chemical toolbox around targeted protein degradation and E3 ligase ligand engineering.

• 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
• Boc-protected amine functionality allows selective deprotection and easy functionalization for PROTAC synthesis.
• Optimized linker length for efficient binding and degradation in CRBN E3 ligase-mediated applications.