(S,R,S)-AHPC-CO-C2-ACID

Background Introduction

(S,R,S)-AHPC-CO-C2-ACID is a specialized E3 ligase ligand-linker conjugate, designed for use in targeted protein degradation technologies such as PROTACs (Proteolysis Targeting Chimeras). This compound features the AHPC moiety—an optimized ligand for recruiting the von Hippel-Lindau (VHL) E3 ubiquitin ligase system—connected via a specific linker structure. E3 ligase ligands play a pivotal role in the design of innovative therapeutic agents by enabling targeted protein degradation, a rapidly emerging strategy in drug discovery.

Mechanism

(S,R,S)-AHPC-CO-C2-ACID functions by binding to the VHL E3 ubiquitin ligase through its AHPC component. When incorporated into a bifunctional PROTAC molecule, this ligand-linker moiety connects to a warhead that recognizes the target protein. The conjugate brings the target protein in close proximity to the E3 ubiquitin ligase, catalyzing ubiquitination of the target and ultimately directing it for proteasomal degradation. The C2 linker provides optimal spatial arrangement, enhancing the efficacy and selectivity of the resulting PROTAC molecules.

Applications

(S,R,S)-AHPC-CO-C2-ACID is widely used in the design and synthesis of VHL-based PROTACs for chemical biology research and early-stage drug discovery. Its applications include development of novel therapeutics against undruggable proteins, validation of new drug targets, and creation of cell-based protein degradation assays. Researchers utilize this ligand-linker conjugate to engineer potent and selective PROTACs tailored for oncology, neurodegeneration, and immune-related diseases, accelerating the pathway from bench to bedside.