(S,R,S)-AHPC-phenol-C4-NH2 dihydrochloride

Background Introduction

(S,R,S)-AHPC-phenol-C4-NH2 dihydrochloride is an advanced E3 ligase ligand-linker conjugate, widely used in targeted protein degradation research, especially within the PROTAC (Proteolysis Targeting Chimera) field. AHPC is a well-established ligand for the Von Hippel-Lindau (VHL) E3 ubiquitin ligase, and the incorporation of a C4 amino linker enables it to be efficiently conjugated with various protein-targeting warheads.

Mechanism

This compound operates as a bifunctional molecule, featuring a high-affinity VHL E3 ligase ligand (AHPC) connected to a flexible C4 linker with a terminal amine group. In PROTAC design, (S,R,S)-AHPC-phenol-C4-NH2 serves as the E3 ligase-recruiting component. When chemically linked to a target protein binder via its amino moiety, it enables the formation of a heterobifunctional PROTAC. Upon cellular entry, the resulting PROTAC induces proximity between the target protein and the VHL E3 ligase, promoting ubiquitination and subsequent proteasomal degradation of the target protein. The dihydrochloride salt enhances solubility and stability for biochemical applications.

Applications

(S,R,S)-AHPC-phenol-C4-NH2 dihydrochloride finds broad use in the construction of VHL-based PROTACs for selective and robust degradation of disease-related proteins. Key applications include: development of chemical probes for target validation, pharmaceutical research for drug discovery and lead optimization, and academic studies exploring novel protein degradation pathways. Its amine-functionalized linker allows easy conjugation with various target-binding molecules, supporting the efficient design and synthesis of customized PROTACs for oncology, neurodegenerative diseases, and epigenetic research.