(S,R,S)-AHPC-C5-COOH (VH032-C5-COOH) is a synthesized conjugate for E3 ligase ligand-linker applications, combining the VH032 VHL-based ligand with a linker for PROTAC development. VH-032 is a selective and potent VHL/HIF-1α interaction inhibitor with a dissociation constant (Kd) of 185 nM, offering potential in anemia and ischemic diseases research[1].

PROTACs are bifunctional molecules consisting of two ligands linked together; one binds to an E3 ubiquitin ligase, and the other targets a specific protein. Through the utilization of the cell's ubiquitin-proteasome system, PROTACs achieve the selective degradation of target proteins. Notably, the von Hippel–Lindau (VHL) tumor suppressor protein functions as the substrate-binding component of the VHL E3 ubiquitin ligase, targeting the hydroxylated α subunit of hypoxia-inducible factors (HIFs) for ubiquitination and subsequent proteasomal degradation.