Thalidomide-5-propargyl

Background Introduction

Thalidomide-5-propargyl is a chemically modified analog of the classic immunomodulatory drug thalidomide, specifically substituted at the 5-position with a propargyl group. This structural modification provides an alkyne functional handle, broadening its versatility for click chemistry and conjugation reactions. As a key ligand for Cereblon (CRBN), an E3 ubiquitin ligase substrate-recognition subunit, thalidomide-5-propargyl plays a vital role in targeted protein degradation (TPD) platforms, most notably in the design and synthesis of CRBN-recruiting PROTACs (Proteolysis Targeting Chimeras).

Mechanism

Thalidomide-5-propargyl specifically binds to the CRBN protein, a core component of the CUL4-CRBN E3 ubiquitin ligase complex. Upon incorporation into a bifunctional molecule (such as a PROTAC), thalidomide-5-propargyl facilitates the recruitment of CRBN to the target protein of interest, driving polyubiquitination and proteasomal degradation. The propargyl (alkyne) group at the 5-position offers a highly reactive site for copper-catalyzed azide-alkyne cycloaddition (CuAAC, or 'click chemistry'), enabling efficient linker attachment and flexible molecular assembly during PROTAC construction.

Applications

Thalidomide-5-propargyl is widely used as a key building block in the synthesis of CRBN-based PROTACs and molecular glue degraders. Its alkyne functionality is ideal for modular click chemistry approaches, expediting SAR studies and enabling rapid analogue synthesis. Key applications include:

• Construction of CRBN-recruiting linkers for PROTAC and heterobifunctional degrader design
• Development of click chemistry-enabled libraries for medicinal chemistry optimization
• Generation of custom protein degraders for drug discovery and mechanistic biology research
• Facilitating site-specific bioconjugation strategies in both academic and pharmaceutical environments

By leveraging its unique chemistry, thalidomide-5-propargyl greatly enhances flexibility and efficiency in next-generation targeted protein degradation 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
• Alkyne functional group enables click chemistry for efficient PROTAC assembly and bioconjugation applications.
• High specificity for CRBN E3 ligase targeting, making it optimal for the design of next-generation targeted protein degraders.