A new molecular glue, CLEO4-88, deactivates target proteins by binding to one protein and inducing a shape change that promotes interaction with a second protein.

The findings were published in Nature Chemical Biology, with the research conducted at the Canadian Light Source, the national lab affiliated with the University of Saskatchewan on Treaty 6 Territory and the Homeland of the Métis.

This approach tackles a major drug design limitation by targeting proteins that lack obvious binding pockets or that mutate, potentially broadening therapeutic options for cancers and metabolic diseases.

The discovery points toward a future where molecular glues can be rationally designed to tune protein activity, aiming for a balance between efficacy and safety by avoiding total loss of function.

High-resolution X-ray measurements at the Canadian Light Source show CLEO4-88 dampens the activity of ACAA1, a fat-processing protein, demonstrating selective regulation rather than complete destruction.