Pomalidomide-d5 is a deuterated analog of pomalidomide, specifically engineered for advanced PROTAC research and proteolysis targeting chimera applications. As an E3 ligase ligand, it binds cereblon (CRBN), a key E3 ubiquitin ligase recruiting component, enabling selective ubiquitination and degradation of pathogenic proteins. The incorporation of five deuterium atoms provides enhanced metabolic stability and facilitates quantitative mass spectrometry in tracer studies. Pomalidomide-d5 is ideal for the synthesis of CRBN-recruiting PROTACs in targeted protein degradation, drug discovery, and mechanistic studies on ubiquitin-proteasome system function.
Structure of 1377838-49-7
* For research and manufacturing use only. Not for human or clinical use.
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Background Introduction
Pomalidomide-d5 is the deuterated form of pomalidomide, a well-characterized immunomodulatory imide drug (IMiD) that serves as a potent ligand for the Cereblon (CRBN) E3 ubiquitin ligase. This stable isotope-labeled analog contains five deuterium atoms, making it a unique tool for pharmacokinetic studies and tracer experiments as well as an effective building block for proteolysis targeting chimera (PROTAC) design. Leveraging the biological activity of pomalidomide, pomalidomide-d5 supports quantitative analysis and advanced research in targeted protein degradation (TPD) technologies.
Mechanism
Pomalidomide-d5 binds selectively to the CRBN component within the CUL4-CRBN E3 ubiquitin ligase complex. Through this CRBN recognition, it mediates the recruitment of the ligase machinery to the protein of interest when incorporated into a PROTAC construct. This recruitment enables targeted ubiquitination and subsequent degradation of the target protein via the proteasomal pathway. The incorporation of deuterium atoms provides enhanced analytical capabilities for mass spectrometry, offering increased stability and facilitating differentiation in metabolic or in vivo studies compared to non-deuterated forms.
Applications
Pomalidomide-d5 serves as a crucial intermediate in the synthesis of CRBN-recruiting PROTACs and molecular glues. Its deuterated nature is especially valuable for ADME (absorption, distribution, metabolism, and excretion) studies, bioanalytical quantification, and tracking the fate of PROTACs in biological systems. Key applications include:
• Synthesis of CRBN-based PROTACs for targeted protein degradation research
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
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