A new drug discovery method to transform peptides to small molecules: proof of principle with p53-hdm2

This Small Business Innovation Research (SBIR) Phase I project will advance an innovative drug discovery technology to tackle important disease targets such as protein-protein interactions. Conventional drug discovery technologies are rarely successful at identifying drugs that can disrupt protein-protein interactions. While peptides can disrupt protein-protein interactions, peptides seldom make good drugs. This proposal describes a powerful approach to transform peptides into drug-like molecules. The well-characterized and important anti-cancer target p53-hdm2 will be used as a model system. Peptide inhibitors of the p53-hdm2 interaction have been described in the literature. The objective of this Phase I proposal is to convert these peptides into drug-like molecules. Subsequently, these molecules can be further advanced into drug candidates for treating human cancers. In addition, successful completion of the proposed research will validate a transformative new drug discovery technology. The broader impacts of this research are to develop the technologies to tackle important human disease targets that are not amenable to current drug-discovery approaches. Protein-protein interactions present one of the largest untapped opportunities to develop new therapies. The technology provides a general and systematic method to tackle this target class by efficiently transforming peptides into small molecules. It has the potential to revolutionize the drug discovery process, and thus the commercial opportunity is enormous. In addition, the proposed technology will advance our understanding of drug discovery. The societal impact will be substantial, as the technology will facilitate the discovery of drugs for unmet medical needs.