Pomalidomide-PEG2-C2-NH2

Background Introduction

Pomalidomide-PEG2-C2-NH2 is a synthetic molecule designed as an E3 ligase ligand-linker conjugate, commonly used in the development of Proteolysis Targeting Chimeras (PROTACs). The pomalidomide moiety specifically recruits the cereblon (CRBN) E3 ubiquitin ligase, while the PEG2-C2-NH2 flexible linker allows for further functionalization and conjugation to target protein ligands. This modular construct plays a crucial role in targeted protein degradation research, which is an emerging therapeutic strategy in drug discovery.

Mechanism

The mechanism of action of Pomalidomide-PEG2-C2-NH2 is based on the ubiquitin-proteasome system. The pomalidomide unit binds selectively to the CRBN E3 ligase, acting as a recruiting element. The PEG2-C2 linker provides an ideal distance and flexibility for bifunctional assembly, enabling the conjugation of a ligand that binds to a protein of interest (POI). Upon formation of a PROTAC molecule, the E3 ligase is brought into close proximity with the POI, leading to ubiquitination of the target protein and its subsequent degradation by the proteasome.

Applications

Pomalidomide-PEG2-C2-NH2 is widely used in the synthesis of novel PROTACs for chemical biology and drug discovery applications. It enables the rapid development of PROTACs targeting a variety of disease-related proteins, including oncogenic kinases, transcription factors, and epigenetic regulators. The product is also valuable in mechanistic studies of ubiquitin-dependent protein degradation, validation of therapeutic targets, and in the development of next-generation therapeutics for cancer, neurodegenerative diseases, and immune disorders.