Pure-DEL

Many proteins that play a central role in disease cannot be targeted effectively with state-of-the-art medicines. This problem is especially evident in hard-to-treat cancers such as pancreatic and colorectal cancer, as well as in many inflammatory diseases, leaving many patients without effective treatment. These proteins are difficult to target because they are often located deep inside cells, making them hard for drugs to reach, and because their shape offers few opportunities for conventional medicines to bind to them. Together, these two challenges represent a major technological barrier in drug discovery.

With Pure-DEL, Pioneer Fellow Michelle Keller and colleagues have developed a platform to identify new treatment options for these difficult-to-target disease proteins. Their approach uses synthetic macrocycles: ring-shaped molecules designed with drug-like properties that may be capable of targeting these challenging proteins. Pure-DEL for the first time makes it possible to physically create billions of these synthetic macrocycles and test all of them together in a single experiment, pinpointing the structures that bind a given protein.

As part of the Pioneer Fellowship, Michelle Keller will test libraries of macrocycles against disease-relevant proteins. Her aim is to identify promising drug candidates, evaluate their effects and prepare the next steps towards establishing a biotech start-up.