Leveraging Large Scale Bioinformatics and AI for Natural Product Drug Discovery and Target Selection

Natural product (NP) small molecules continue to be a prolific source for therapeutic drug innovation, yet NP discovery is constrained by persistent challenges. These include the frequent rediscovery of known compounds and the inability to predict interactions between NPs and biological targets, particularly when dealing with novel or poorly characterized compounds or targets. Evoquant LLC is working to address this challenge through the development of BioPredictor™, an innovative platform that leverages cutting-edge artificial intelligence (AI), integrated with multi-omics knowledge graphs at a multi-repository scale. BioPredictor™ is designed to modernize NP drug discovery by enabling the prediction of NP interactions with biological targets, especially where existing methods cannot. The project is organized around three specific aims: (1) to refine and scale the BioPredictor™ platform by integrating advanced AI/ML algorithms capable of handling large-scale, complex datasets; (2) systematically prioritize biosynthetic gene clusters and microbial strains for laboratory validation based on their potential to yield novel therapeutics; and (3) to conduct rigorous phenotypic and target-specific assays that will validate the platform’s predictions and confirm their relevance to therapeutic development. This project promises to accelerate the discovery and application of novel therapeutics by significantly enhancing prediction of NP bioactivity, particularly for conditions with high unmet medical needs, such as rare diseases and cancers. The successful implementation of the BioPredictor™ platform will represent a paradigm shift in NP drug discovery, moving the field away from reliance on serendipity and towards a more systematic and predictive approach. This project aligns directly with NIH priorities by advancing translational research, supporting the development of treatments that target molecular pathways common to multiple diseases, and contributing to the broader NIH mission of accelerating the development of new therapies to improve health outcomes and reduce the burden of disease. The outcomes of this work have the potential to significantly impact the future of drug discovery, leading to more effective treatments.