(S,R,S)-AHPC-C2-NH2 dihydrochloride

Background Introduction

(S,R,S)-AHPC-C2-NH2 dihydrochloride is a versatile E3 ligase ligand-linker conjugate designed specifically for PROTAC (Proteolysis Targeting Chimera) technology. By incorporating the AHPC (aryl hydroxyproline carboxamide) moiety, this molecule efficiently recruits the von Hippel-Lindau (VHL) E3 ubiquitin ligase, enabling targeted protein degradation. As a functionalized warhead with a reactive amine group and a dihydrochloride salt for enhanced solubility, (S,R,S)-AHPC-C2-NH2 serves as an essential building block in next-generation drug discovery research and targeted protein degradation applications.

Mechanism

The mechanism of (S,R,S)-AHPC-C2-NH2 dihydrochloride centers on its role as the E3 ligase-binding arm in bifunctional PROTAC molecules. The AHPC motif selectively binds to the VHL E3 ligase complex, while the C2-linked primary amine provides a handle for conjugating target protein ligands via amide bond formation. Upon cellular entry, PROTACs constructed with (S,R,S)-AHPC-C2-NH2 bring the E3 ligase and target protein into proximity. This facilitates ubiquitination and proteasomal degradation of the target, driving potent and selective protein knockdown.

Applications

(S,R,S)-AHPC-C2-NH2 dihydrochloride is widely used in the custom synthesis of PROTAC molecules for targeted protein degradation studies. Its applications span early-stage drug discovery, functional genomics, and validation of novel drug targets. Scientists use this ligand-linker conjugate to streamline the development of PROTAC libraries against disease-associated proteins, enabling rapid screening and structure-activity relationship (SAR) exploration. Its reliable E3 ligase recruitment makes it highly valuable for both academic research and pharmaceutical development in the emerging field of targeted protein degradation.