Pomalidomide-C7-NH2 hydrochloride

Background Introduction

Pomalidomide-C7-NH2 hydrochloride is a bifunctional molecule designed as an E3 ligase ligand-linker conjugate. It integrates the immunomodulatory drug (IMiD) pomalidomide, which binds to the cereblon (CRBN) E3 ubiquitin ligase, with a seven-carbon (C7) flexible linker terminating in an amine group. This compound is commonly utilized in the development and synthesis of PROTACs (proteolysis targeting chimeras) for targeted protein degradation applications. By providing a functionalized pomalidomide moiety, it enables researchers to conveniently assemble chimeric molecules that harness the body's natural protein degradation machinery.

Mechanism

Pomalidomide-C7-NH2 hydrochloride operates by recruiting the cereblon E3 ubiquitin ligase to the target protein-of-interest via a linker and a ligand specific to the target. The pomalidomide portion anchors the molecule to the CRBN E3 ligase, while the linker (C7-NH2) offers flexibility for further chemical conjugation. Upon connecting to a targeting ligand, the resulting PROTAC bridges the E3 ligase to the target protein, initiating ubiquitination. This ubiquitination marks the protein for recognition and degradation by the proteasome, leading to selective depletion of disease-associated or pathogenic proteins in cells.

Applications

Pomalidomide-C7-NH2 hydrochloride is widely used as a building block in PROTAC technology, aiding researchers in the creation of custom degraders for drug discovery, chemical biology, and therapeutic research. Its primary applications include development of targeted protein degradation systems, mechanistic studies of protein function, validation of drug targets, and exploration of novel therapeutics for diseases such as cancer, neurodegenerative disorders, and autoimmune conditions. The functional amine group enables straightforward conjugation to a diverse array of targeting ligands, making it a highly versatile tool for the rapid synthesis of new PROTAC molecules.

• Long aliphatic C7 linker provides improved spatial flexibility for efficient ternary complex formation in PROTAC applications.
• Amine-terminated conjugate is specifically optimized for high-yield CRBN E3 ligase ligand incorporation in targeted protein degradation research.