(S,R,S)-AHPC-C6-NH2

Background Introduction

(S,R,S)-AHPC-C6-NH2 is a versatile E3 ligase ligand-linker conjugate widely used in the development of PROTACs (Proteolysis Targeting Chimeras). This innovative small molecule combines a VHL (von Hippel-Lindau) E3 ligase binder with a customizable amine-terminated linker, enabling targeted protein degradation — a revolutionary approach in chemical biology and drug discovery.

Mechanism

(S,R,S)-AHPC-C6-NH2 functions as a bifunctional molecule. The AHPC motif serves as a high-affinity ligand for the VHL E3 ubiquitin ligase complex. The C6 alkyl linker, terminating in a primary amine (-NH2), provides a functional site for conjugation to target protein ligands. When assembled into a PROTAC, (S,R,S)-AHPC-C6-NH2 facilitates the recruitment of VHL to a protein of interest, resulting in its ubiquitination and subsequent proteasomal degradation. This induced proximity underpins the highly specific and catalytic mode of action of PROTAC-based therapeutics.

Applications

(S,R,S)-AHPC-C6-NH2 is widely utilized for constructing PROTACs targeting a broad range of disease-related proteins, including kinases, transcription factors, and epigenetic regulators. Its design flexibility, due to the amine handle, makes it ideal for custom PROTAC synthesis via amide coupling with various target warheads. This reagent accelerates research in chemical biology, drug discovery, and therapeutic development, paving the way for next-generation treatments for cancer, neurodegeneration, and other chronic diseases.

• Amine-terminated C6 linker ensures versatile conjugation for seamless E3 ligase ligand incorporation.
• Engineered for high-affinity interaction with VHL in targeted PROTAC design, enabling efficient protein degradation pathways.