Thalidomide 5-fluoride

Background Introduction

Thalidomide 5-fluoride is a fluorinated analog of thalidomide and belongs to the class of immunomodulatory imide drugs (IMiDs), which are commonly employed as E3 ligase ligands in PROTAC (Proteolysis Targeting Chimera) platforms. The introduction of a fluorine atom at the 5-position on the thalidomide scaffold enhances its physicochemical properties, such as metabolic stability and lipophilicity, making it a valuable building block for the design of next-generation protein degraders. This compound is widely used as a key intermediate in drug discovery and targeted protein degradation research.

Mechanism

Thalidomide 5-fluoride functions as a ligand for the Cereblon (CRBN) E3 ubiquitin ligase, which is a critical component in the CUL4-CRBN E3 ubiquitin ligase complex. By binding to CRBN, this ligand facilitates the recruitment of the E3 ligase to the target protein when linked to an appropriate targeting moiety via a chemical linker. This proximity-driven mechanism enables effective ubiquitination and subsequent proteasomal degradation of the target protein. The 5-fluoro substitution may improve binding affinity, metabolic stability, and tuning of the molecular properties for PROTAC molecule optimization.

Applications

Thalidomide 5-fluoride is widely used in the synthesis of CRBN-based PROTACs and other targeted protein degradation modalities. Its enhanced stability and binding properties make it ideal for:

• Designing and synthesizing next-generation CRBN E3 ligase ligands for improved PROTAC performance
• Constructing bifunctional degraders for efficient and selective targeted protein degradation in drug discovery
• Structure-activity relationship (SAR) studies to examine the effects of fluorination on degrader properties and biological activity
• Custom PROTAC development and lead optimization in pharmaceutical research and academic projects.

• 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
• 5-Fluoride modification enhances binding affinity and selectivity for CRBN E3 ligase.
• Optimal for designing next-generation CRBN-recruiting PROTACs with improved pharmacokinetic properties.