Pomalidomide-C3-I

Background Introduction

Pomalidomide-C3-I is a state-of-the-art E3 ligase ligand-linker conjugate designed for use in targeted protein degradation research. As an essential building block in PROTAC (Proteolysis Targeting Chimera) technology, this molecule features pomalidomide—a thalidomide analog recognized for its binding to the E3 ubiquitin ligase cereblon (CRBN)—connected via a three-carbon (C3) linker. Its modular design facilitates the rapid development of next-generation PROTACs and molecular glues for both academic and drug discovery applications.

Mechanism

The mechanism of action of Pomalidomide-C3-I centers on leveraging the ubiquitin-proteasome system. The pomalidomide moiety effectively recruits the CRBN E3 ubiquitin ligase complex, while the C3 linker provides a versatile handle for conjugation to a ligand targeting the protein of interest. Once incorporated into a PROTAC molecule, Pomalidomide-C3-I mediates proximity-induced ubiquitination, resulting in selective proteasomal degradation of the target protein. This innovative approach enables the removal of disease-relevant or hard-to-drug proteins at the post-translational level, differentiating PROTACs from traditional small-molecule inhibitors.

Applications

Pomalidomide-C3-I is widely utilized as a chemical intermediate for designing and synthesizing CRBN-based PROTACs and related heterobifunctional degraders. It supports target identification, lead optimization, and mechanistic studies in preclinical research. Applications include advancing cancer therapy, neurodegenerative disease models, and other pathogenic contexts where selective protein knockdown is desirable. Additionally, Pomalidomide-C3-I is valuable for academic research exploring targeted protein degradation pathways and structure-activity relationship (SAR) profiling of novel degrader molecules.