Fragment-Based Screening to Identify Novel Fragment Hits for VHL-Elongin B/C Complex

Von Hippel-Lindau (VHL) is one of the most commonly used E3 ligases in bifunctional degraders such as PROTACs. While these molecules hold significant therapeutic promise, their size and complexity pose challenges in developing orally bioavailable compounds. At Sygnature Discovery, we’ve applied a fragment-based screening approach to identify novel VHL binders that could provide alternative starting points for developing next-generation degraders.

About the Study

Leveraging our proprietary fragment library and the Biacore 8K+ platform, we conducted high-throughput screening against the VHL-Elongin B/C (VCB) complex to:

  • Explore new chemical vectors beyond established ligands
  • Identify fragment hits suitable for medicinal chemistry expansion
  • Enhance the efficiency of early stage-PROTAC development

Our curated library design and advanced clean-screening workflows enable rapid progression from fragment screening to hit optimization.

Technology Spotlight

The Biacore 8K+ system plays a central role in our fragment screening capabilities, offering:

  • High-throughput screening for fragments
  • Exceptional sensitivity for weak binders
  • Streamlined follow-up profiling for faster decision-making

This integrated workflow accelerates the delivery of high-quality starting points for downstream medicinal chemistry programmes.

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