Randomized trial identifies cyclic vinyl sulfones as effective WRN inhibitors in tumors with high microsatellite instability, indicating potential therapeutic strategies.
Key Points
The aim is to design cyclic vinyl sulfones that serve as covalent inhibitors of WRN.
Identified noncovalent WRN inhibitors suitable for modification.
Designed cyclic vinyl sulfones to enhance covalent binding to WRN.
Evaluated efficacy of these compounds in tumor models with high microsatellite instability.
Cyclic vinyl sulfones showed significant inhibition of WRN activity.
In MSI-H tumors, pharmacological inhibition led to reduced tumor viability.
Demonstrated enhanced binding affinity compared to existing noncovalent inhibitors.