Nutlin-C1-amido-PEG4-C2-N3

Background Introduction

Nutlin-C1-amido-PEG4-C2-N3 is a specially engineered E3 ligase ligand-linker conjugate designed for use in the development of Proteolysis Targeting Chimeras (PROTACs). This compound features a Nutlin-based ligand that specifically binds the MDM2 E3 ligase, connected to an azide-terminated polyethylene glycol (PEG4) linker. The modular design of Nutlin-C1-amido-PEG4-C2-N3 enables researchers to create custom PROTAC molecules for targeted protein degradation applications.

Mechanism

The mechanism of Nutlin-C1-amido-PEG4-C2-N3 centers on targeted protein degradation via the ubiquitin-proteasome system. When incorporated into a bifunctional PROTAC molecule, the Nutlin moiety binds to the MDM2 E3 ubiquitin ligase, while the azide group at the end of the PEG4 linker allows for click chemistry attachment to a ligand that targets the protein of interest. Upon binding both the E3 ligase and the target protein, the PROTAC induces proximity-driven ubiquitination of the target, marking it for proteasomal degradation and thereby reducing its cellular levels.

Applications

Nutlin-C1-amido-PEG4-C2-N3 is widely used in the research and development of novel PROTACs aimed at selective protein degradation. Its MDM2-targeting capability makes it especially suitable for applications in oncology, cell signaling, and protein homeostasis studies. Researchers use Nutlin-C1-amido-PEG4-C2-N3 to design and synthesize next-generation small molecules for target validation, drug discovery, and the exploration of disease-relevant signaling pathways. Additionally, the azide functionality enables easy conjugation with a wide range of ligands, offering flexibility in designing PROTACs for customized therapeutic or research purposes.

• Nutlin-derived ligand ensures high affinity and selectivity for MDM2, enabling effective targeted protein degradation in PROTAC applications.
• PEG4 linker and terminal azide group provide superior solubility and versatile conjugation options for customizable PROTAC design and bioconjugation strategies.