(S,R,S)-AHPC-C6-PEG3-C4-Cl

Background Introduction

(S,R,S)-AHPC-C6-PEG3-C4-Cl is a specialized E3 ligase ligand-linker conjugate, designed for use in the development of PROTACs (Proteolysis Targeting Chimeras) and targeted protein degradation technologies. The compound incorporates an optimized von Hippel-Lindau (VHL) ligand (AHPC) framework linked by a flexible PEG3-based linker, making it a versatile building block for innovative drug discovery and chemical biology research.

Mechanism

The mechanism of action for (S,R,S)-AHPC-C6-PEG3-C4-Cl centers on its role as an E3 ligase recruiter in PROTAC molecule design. The AHPC moiety binds selectively to the VHL E3 ubiquitin ligase complex, enabling the recruitment of the cellular degradation machinery. The PEG3-C6-C4 linker provides spatial flexibility for the conjugation of various target protein ligands via the terminal chloride group. Once a target ligand is attached and the final PROTAC is formed, it simultaneously engages the target protein and the VHL ligase, promoting ubiquitination and subsequent proteasomal degradation of the target protein.

Applications

(S,R,S)-AHPC-C6-PEG3-C4-Cl is widely used in medicinal chemistry and chemical biology research for the synthesis of PROTACs targeting diverse disease-relevant proteins. Its customizable linker and reactive chloride group enable the rapid development of bifunctional molecules for preclinical studies in oncology, neurology, and immunology. The product is particularly valuable for structure-activity relationship (SAR) studies, target validation, and the creation of next-generation protein degradation therapeutics, facilitating advances in drug discovery where traditional inhibitors may not suffice.

• Versatile PEGylated linker design improves solubility and pharmacokinetics in PROTAC development.
• AHPC-based ligand ensures high-affinity VHL E3 ligase recruitment, enabling efficient target protein degradation.