PhoreMost Limited, a UK-based biopharmaceutical company dedicated to drugging ‘undruggable’ disease targets, and algorithm-driven artificial intelligence (AI)-based pharmaceutical technology company XtalPi Inc have entered into a drug discovery collaboration in which they will aim to rapidly identify and develop compounds to advance a drug discovery programme against targets that epigenetically regulate tumour progression and have been previously classified as ‘undruggable’. The companies will pursue this aim with a unique combination of machine learning and physics-based computation methods using XtalPi’s intelligent digital drug discovery and development (ID4) platform to explore novel sites discovered by PhoreMost’s SITESEEKER platform.

PhoreMost’s SITESEEKER platform exploits protein shape diversity to find new peptide targets, significantly enhancing the power of phenotypic screening and translation into therapeutic modalities. Based on its proprietary protein interference technology, PROTEINi, PhoreMost uses SITESEEKER to probe the entire proteome in a live cell environment for novel druggable targets linked to any chosen disease. This enables the systematic discovery of functionally active peptides that are directly linked to useful therapeutic applications.

Protein-protein interaction sites are traditionally considered ’undruggable’ by small molecules due to their large flat surface and the absence of well-defined binding pockets. XtalPi’s ID4 platform integrates data-driven AI models with physics-based methods to quickly ‘distil’ a small number of high-quality compounds from an AI-generated target-specific chemical space that includes millions of diverse molecules. The companies state that such diversity, combined with the speed and accuracy of ID4’s drug property prediction algorithms, allows scientists to identify promising candidates, overcome the bottleneck of simultaneously optimizing all pharmacological properties, and ensure a smooth progression into preclinical and clinical studies.