Developing a cytoskeleton-targeted small molecule inhibitor for Coccidiosis

The goal of this USDA NIFA SBIR Phase I project is to develop Kainomyx's small-molecules into effective potent and safe anti-coccodials for use in poultry farms. Coccidiosis is caused by Eimeria parasites and is a highly destructive intestinal disease that affects the poultry industry and represents an economic cost estimated at $14.5 billion worldwide. Presently several anticoccidial products including ionophores and antibiotics are used but drug resistance has become a significant issue. Kainomyx's novel small-molecule inhibitors target parasite cytoskeletal proteins and are not considered ionophoric nor antibiotic. Cytoskeletal proteins play a crucial role in various parasite functions such as motion force-generation and parasite motility. These parasite functions are essential in multiple stages of parasite infection including movement of the parasite host cell invasion and development. Our preliminary compounds inhibit the cytoskeletal protein target biochemically and reduce parasite development in host cells. These initial compounds display highly desirable properties in the hit-to-lead pipeline including physio-chemical properties such as high target selectivity and low host cell toxicity. Our goal is to progress early compounds to early lead inhibitors. We will do this through analysis of structure-activity-relationships between proteins and inhibitory compounds. We will identify diverse novel chemotypes which cause biochemical inhibition and cellular inhibition and progress these inhibitors from in vitro pharmacological and therapeutic evaluations to in vivo assessments of their effectiveness pharmacokinetics and pharmacodynamics in experimental chicken models of coccidiosis. This will significantly enhance the landscape for coccidiosis prophylaxis and therapeutics.