Pomalidomide-C3-CO2H

Background Introduction

Pomalidomide-C3-CO2H is a specialized E3 ligase ligand-linker conjugate designed for use in the development of PROTACs (Proteolysis Targeting Chimeras). It incorporates pomalidomide, a well-established ligand for the cereblon (CRBN) E3 ubiquitin ligase, linked via a three-carbon (C3) linker terminating in a carboxylic acid (CO2H). This design facilitates straightforward conjugation to various target protein ligands, making it a versatile tool in drug discovery and targeted protein degradation research.

Mechanism

Pomalidomide-C3-CO2H operates as a critical building block in PROTAC technology. The pomalidomide moiety binds selectively to the CRBN substrate receptor, a component of the CRL4CRBN E3 ubiquitin ligase complex. The C3 alkyl linker enables flexible spatial arrangement, while the terminal carboxyl group provides a functional handle for coupling with amines on target-binding ligands. When incorporated into a PROTAC molecule, Pomalidomide-C3-CO2H facilitates the recruitment of the CRBN E3 ligase to a designated target protein, leading to its polyubiquitination and subsequent proteasomal degradation.

Applications

Pomalidomide-C3-CO2H is widely utilized in the synthesis of CRBN-based PROTACs for both in vitro and in vivo studies. Its applications include targeted degradation of disease-associated proteins in oncology, neurology, and immunology research. The carboxyl-functionalized linker enables easy and efficient conjugation to a broad range of ligands, enhancing the adaptability of PROTAC design and accelerating drug discovery efforts. This reagent is also valuable in academic and pharmaceutical research aiming to validate new therapeutic targets and elucidate the mechanisms of protein homeostasis via induced protein degradation.