(S,S,S)-AHPC hydrochloride

Background Introduction

(S,S,S)-AHPC hydrochloride (also known as (S)-(+)-3-(2-(3-(4-Chlorophenyl)-1-methyl-1H-pyrazol-5-yloxy)ethyl)-3-((S)-2-hydroxypropanamido)azetidine-1-carboxylic acid hydrochloride) is a potent and selective ligand designed for targeting the von Hippel-Lindau (VHL) E3 ubiquitin ligase. VHL ligands, such as AHPC, have become key tools in the field of targeted protein degradation, particularly in the development of PROTACs (Proteolysis Targeting Chimeras). This compound provides a robust handle for recruiting VHL E3 ligase to facilitate degradation of disease-relevant proteins.

Mechanism

(S,S,S)-AHPC hydrochloride selectively binds to the VHL E3 ubiquitin ligase component, specifically recognizing and attaching to the VHL protein. When incorporated as the E3 ligase recruiting element in a PROTAC, it brings VHL into close proximity with a target protein, which is tethered via another ligand or warhead. The resulting ternary complex (target-PROTAC-VHL) enables VHL to ubiquitinate the target protein, thereby marking it for recognition and degradation by the 26S proteasome. The hydrochloride form of AHPC enhances its solubility, handling, and stability for chemical conjugation.

Applications

(S,S,S)-AHPC hydrochloride is widely used in the synthesis of VHL-based PROTAC molecules for chemical biology and drug discovery. It serves as a key building block for the construction of bifunctional molecules designed to induce degradation of pathogenic or undruggable proteins. Common applications include:

• Development of VHL-recruiting PROTACs targeting oncoproteins, transcription factors, and kinases
• Target validation studies by selective degradation of proteins of interest
• Structure-activity relationship (SAR) exploration for PROTAC optimization
• Synthesis of custom small molecule degraders for preclinical and academic research
• Evaluation of E3 ligase ligand scope, selectivity, and pharmacokinetics in medicinal chemistry projects.

• High-purity compound verified by HPLC, NMR, and LC-MS
• Consistent batch-to-batch reproducibility with complete QC documentation
• Supplied with COA, MSDS, and analytical data for traceability
• Reliable global shipping with stability-guaranteed packaging
• Dedicated technical support and optional custom synthesis service
• Demonstrates strong binding affinity to CRBN, VHL, or other E3 ligases
• Enables stable E3 ligase recruitment for targeted protein degradation
• Highly selective VHL E3 ligase ligand for targeted protein degradation applications
• Hydrochloride salt form ensures excellent solubility and ease of use in PROTAC synthesis