Pomalidomide-C6-CO2H

Background Introduction

Pomalidomide-C6-CO2H is a specialized E3 ligase ligand-linker conjugate widely utilized in the development of PROTACs (Proteolysis Targeting Chimeras). By combining pomalidomide, a cereblon (CRBN) ligand, with a functionalized C6 alkyl linker terminated with a carboxylic acid (CO2H) group, this molecule serves as a powerful intermediate in targeted protein degradation research.

Mechanism

Pomalidomide-C6-CO2H operates by harnessing the body's ubiquitin-proteasome system (UPS) for selective protein degradation. In PROTAC construction, the pomalidomide moiety binds to the CRBN E3 ubiquitin ligase, while the reactive carboxylic acid permits further conjugation to other ligands, such as target protein binders. Upon successful linking, the resulting PROTAC molecule brings the E3 ligase and the target protein into close proximity, facilitating ubiquitination of the target and subsequent proteasomal degradation.

Applications

Pomalidomide-C6-CO2H is primarily used as a chemical building block in the design and synthesis of PROTACs and molecular glues to explore targeted protein degradation. Its applications include discovery research for novel therapeutics, functional genomics studies, target validation, and the development of next-generation protein degraders aimed at treating cancers, neurodegenerative diseases, and immunological disorders. The compound’s carboxyl-terminated linker allows flexible conjugation chemistry, making it ideal for constructing diverse proteolytic targeting molecules and for customizing linker lengths to optimize activity and selectivity in probe or drug development.