Searchlight leverages a proprietary, computationally designed library of non-fragment, drug-like molecules to “probe” the proteome and identify binding pockets. All screens are conducted in a native cellular environment to ensure that no binding pocket is missed. The platform leverages reversible (non-covalent) binding interactions, a differentiating feature versus other chemoproteomic platforms which rely on irreversible binding. The majority of approved medicines are non-covalent typically leading to a more tolerable safety profile and fewer risks for development.

When a drug-like probe molecule reversibly binds to a protein, the Searchlight Platform uses photoaffinity chemistry to crosslink the probe to the bound protein. With exposure to ultraviolet light, the probe gets locked into place, enabling our team to identify which proteins are bound by the probe as well as the precise binding location on the target proteins. The site-of-labeling information allows us to rapidly understand the location and features of the pocket, greatly enabling medicinal chemistry optimization.

To date, our team has identified more than 4,000 binding pockets for the undrugged proteome. With these data and insights in hand, we have more informed, de-risked starting points to design and advance first-in-class and best-in-class medicines across a range of diseases and unmet patient needs. In addition, the proprietary proteome maps and site-of-labeling data are being leveraged to inform our machine learning and generative AI strategies and ultimately further augment platform performance.