N-Methylated pomalidomide

Background Introduction

N-Methylated pomalidomide is a structural analog of the immunomodulatory drug pomalidomide, which is part of the thalidomide family used as E3 ligase ligands in targeted protein degradation technologies. By methylating the amide nitrogen, this derivative modulates the binding affinity and selectivity for the Cereblon (CRBN) E3 ubiquitin ligase complex, offering unique chemical and biological characteristics that can be leveraged in the design of PROTACs (Proteolysis Targeting Chimeras) and related degrader molecules.

Mechanism

N-Methylated pomalidomide retains the core glutarimide moiety responsible for Cereblon binding but introduces a methyl group to the amide nitrogen, reducing the overall hydrogen-bond donor capacity. This modification alters its interaction profile with the CRBN pocket, potentially affecting substrate specificity and reducing off-target effects. When incorporated into bifunctional degraders like PROTACs, N-Methylated pomalidomide enables recruitment of CRBN for the ubiquitination and proteasomal degradation of target proteins, but with a potentially altered safety and efficacy profile due to its unique chemical properties.

Applications

N-Methylated pomalidomide is widely employed in PROTAC research and drug discovery:

• Advancement of CRBN-based PROTAC designs to explore structure-activity relationships (SAR) and minimize off-target effects associated with classical IMiDs.
• Development of next-generation molecular glues with improved selectivity for target proteins, providing new therapeutic avenues. • Use as a synthetic intermediate for custom ligand-linker conjugation in degrader optimization and medicinal chemistry programs. • Application in academic and commercial research to expand the toolbox of E3 ligase ligands for exploring novel protein degradation paradigms.

• 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
• Enhanced plasma stability due to N-methylation, leading to improved pharmacokinetics in PROTAC applications.
• Selective CRBN E3 ligase binding, minimizing off-target effects in targeted protein degradation projects.