Pomalidomide-C9-CO2H

Background Introduction

Pomalidomide-C9-CO2H is a specially designed E3 ligase ligand-linker conjugate that incorporates pomalidomide as the cereblon (CRBN) ligand, a flexible C9 alkyl linker, and a terminal carboxylic acid group for easy conjugation. This advanced reagent is widely used in the development of PROTACs (Proteolysis Targeting Chimeras) to facilitate targeted protein degradation, enabling researchers to create highly efficient and selective chemical probes for various biological targets.

Mechanism

The mechanism of action of Pomalidomide-C9-CO2H revolves around its role as a modular building block in PROTAC synthesis. Pomalidomide binds to the CRBN E3 ubiquitin ligase, recruiting it to the target protein when conjugated to a suitable ligand. The C9 linker offers optimal spatial flexibility, enhancing the formation of the E3 ligase-target protein complex. The terminal carboxylic acid group enables straightforward coupling with amine-containing ligands of interest, enabling rapid assembly of bifunctional molecules that harness the cellular ubiquitin-proteasome pathway to degrade target proteins selectively.

Applications

Pomalidomide-C9-CO2H is extensively used in medicinal chemistry, chemical biology, and drug discovery for the synthesis of PROTACs targeting diverse proteins such as kinases, transcription factors, and epigenetic regulators. Its utility extends to in vitro and in vivo studies to investigate target protein function, validate novel targets, and develop next-generation therapeutics for diseases like cancer, neurodegeneration, and autoimmune disorders. This E3 ligase ligand-linker conjugate streamlines the PROTAC design process, reducing synthetic complexity and accelerating the translation of protein degradation strategies from bench to bedside.

• Carboxyl-functionalized linker enables versatile and efficient coupling to target ligands or payloads.
• Ideal for building high-performance CRBN-based PROTACs with extended linker flexibility for improved target engagement.