Abstract 998: HEx: A computational and synthetic biology platform applied to oncology drug discovery

We present a computational and synthetic biology platform for producing novel compounds targeting proteins relevant to oncology. As eukaryotes, fungi share approximately one third of human genes, including many relevant to core metabolism, cell cycle, DNA repair, and protein degradation. We have developed a computational method for mining fungal genomes to identify genes likely to produce compounds that inhibit specific human target proteins, including undruggable targets such as protein-protein interactions. We engineer these genes using our synthetic biology pipeline to produce the novel compounds in a heterologous host. We present in vitro data for an Aurora Kinase (AURKA) inhibitor developed using this platform as proof of concept for Hexagon Bio9s pipeline. These data demonstrate the potential of this system to target the more than 6000 genes shared between fungi and humans. Citation Format: Ulrich Schlecht, Pablo Cordero, Maureen Hillenmeyer, Ju Eun Jeon, Dan Kvitek, Brian Naughton, Philipp Wiemann, Colin Harvey. HEx: A computational and synthetic biology platform applied to oncology drug discovery [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 998.