Small molecule BODIPY FL VH032 probe for E3 ligase (SJ-21-0014)

St. Jude Reference #SJ-21-0014

Description

Proteolysis Targeting Chimeras, or PROTACs, are heterobifunctional small molecules composed of two active domains and a linker capable of removing specific unwanted proteins. They are being broadly pursued for next generation drugs. Successful PROTAC development depends on ligands of E3 ligases, and they commonly include cereblon, von Hippel−Lindau protein (VHL) and MDM2, because of the availability of their ligands.

Assays are needed to develop novel ligands for VHL but only a peptide-based fluorescent probe is available for VHL. Researchers at St. Jude developed the first small molecule-based fluorescent probe (named BODIPY FL VH032) that is a high-affinity binder to VHL and used it to develop sensitive and selective TR-FRET and FP assays. This probe and assays can be used in high throughput screening to identify novel VHL ligands. The potential commercial applications include using the novel probe for assay development, new assays for high-throughput compound screening, and ultimately lead to more PROTAC-related projects.

The main advantage of this probe compared to peptide-based probes is its high affinity which enables the development of TR-FRET assays that are more sensitive in detecting ligands with various binding affinity.

Keywords

Proteolysis Targeting Chimeras, PROTACs, E3 ligases, von Hippel−Lindau protein (VHL), Diagnostic, TR-FRET assay, FP assay, high throughput screening, Targeted Protein Degradation (TPD), hereditary cancer

Granted patents or published applications

Related scientific references

Wenwei Lin, Yongtao Li, Lei Yang, and Taosheng Chen; “Development of BODIPY FL VH032 as a High-Affinity and Selective von Hippel–Lindau E3 Ligase Fluorescent Probe and Its Application in a Time-Resolved Fluorescence Resonance Energy-Transfer Assay.” ACS Omega 2021 6 (1), 680-695. DOI: 10.1021/acsomega.0c05221

Licensing opportunities

We are seeking a partner to commercialize this probe, develop assays and improve PROTAC development. Contact: chad.riggs@stjude.org.

Contact the Office of Technology Licensing (Phone: 901-595-2342, Fax: 901-595-3148) for more information.