Proteins exposed on the external surface of the cell membrane comprise the majority of targets for approved drugs. Therapeutic modalities that are commonly used to target cell surface proteins include monoclonal antibodies and small molecules that inhibit enzymatic functions. The biotechnology company Evotec is taking a different approach, with their drug discovery platform TargetAlloMod, which identifies small molecules that target cell surface proteins through a novel mechanism; rather than binding to the active site, these compounds bind allosterically to cell surface proteins, inducing a conformational shift that results in proteolytic cleavage and shedding of the target protein.
The Mark Foundation for Cancer Research has partnered with Evotec to develop the TargetAlloMod platform for the discovery and development of first-in-class therapeutics for immuno-oncology. The platform is being used to find small molecules that induce protein shedding via allosteric interaction with validated and novel immuno-oncology targets. This project is a powerful example of The Mark Foundation’s industry partnership model and has the potential to identify the next generation of immuno-oncology drugs, including novel immune checkpoint inhibitors, for use across a wide range of human cancers.