Pomalidomide-PEG3-CO2H

Background Introduction

Pomalidomide-PEG3-CO2H is a specialized E3 ligase ligand-linker conjugate designed for use in PROTAC (Proteolysis Targeting Chimera) technology. PROTACs are bifunctional molecules that harness the cellular ubiquitin-proteasome system to selectively degrade target proteins. This conjugate features pomalidomide, a cereblon (CRBN) E3 ligase recruiter, connected via a flexible PEG3 linker to a carboxylic acid functional group, making it an ideal intermediate for constructing novel PROTAC molecules.

Mechanism

Pomalidomide-PEG3-CO2H operates through a unique mechanism of action. The pomalidomide unit specifically binds to the CRBN component of the E3 ubiquitin ligase complex. The PEG3 linker provides optimal spatial arrangement and improved solubility, while the terminal carboxylic acid group facilitates coupling to various target protein ligands. When incorporated into a PROTAC, this conjugate enables the proximity-induced ubiquitination of the target protein, leading to its subsequent degradation by the proteasome.

Applications

Pomalidomide-PEG3-CO2H serves as a versatile building block in PROTAC research and development. It finds broad use in the synthesis of novel protein degraders for therapeutic, drug discovery, and chemical biology applications. By enabling the targeted degradation of disease-related proteins, PROTACs derived from this conjugate have potential in cancer research, neurodegenerative diseases, and other areas where protein modulation is crucial. Additionally, the conjugate's carboxylic group allows straightforward attachment to a diverse range of ligands, significantly accelerating the generation and optimization of custom PROTAC libraries.

• Polyethylene glycol (PEG3) linker improves aqueous solubility and bioavailability of PROTAC molecules.
• Carboxylic acid (CO2H) functional group enables efficient conjugation for CRBN E3 ligase-based PROTAC development.