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Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis

2017; Elsevier BV; Volume: 47; Issue: 12 Linguagem: Inglês

10.1016/j.ijpara.2017.08.006

1879-0135

Matthew A. Hulverson, Ryan Choi, Samuel L.M. Arnold, Deborah A. Schaefer, Andrew Hemphill, Molly C. McCloskey, Dana P. Betzer, Joachim Müller, Rama Subba Rao Vidadala, Grant R. Whitman, Kasey Rivas, Lynn K. Barrett, Robert C. Hackman, Melissa S. Love, Case W. McNamara, Thomas K. Shaughnessy, Alison Kondratiuk, Matthew D. Kurnick, Patricia N. Banfor, James J. Lynch, Gail M. Freiberg, Dale J. Kempf, Dustin J. Maly, Michael W. Riggs, Kayode K. Ojo, Wesley C. Van Voorhis,

Parasitic Infections and Diagnostics

Improvements have been made to the safety and efficacy of bumped kinase inhibitors, and they are advancing toward human and animal use for treatment of cryptosporidiosis. As the understanding of bumped kinase inhibitor pharmacodynamics for cryptosporidiosis therapy has increased, it has become clear that better compounds for efficacy do not necessarily require substantial systemic exposure. We now have a bumped kinase inhibitor with reduced systemic exposure, acceptable safety parameters, and efficacy in both the mouse and newborn calf models of cryptosporidiosis. Potential cardiotoxicity is the limiting safety parameter to monitor for this bumped kinase inhibitor. This compound is a promising pre-clinical lead for cryptosporidiosis therapy in animals and humans.