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

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

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)753-763
Number of pages11
JournalInternational Journal for Parasitology
Volume47
Issue number12
DOIs
StatePublished - Oct 2017

Keywords

  • BKI 1369
  • Calcium-dependent protein kinase 1
  • Cryptosporidiosis
  • Drug target
  • Gatekeeper residue

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

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    Hulverson, M. A., Choi, R., Arnold, S. L. M., Schaefer, D. A., Hemphill, A., McCloskey, M. C., Betzer, D. P., Müller, J., Vidadala, R. S. R., Whitman, G. R., Rivas, K. L., Barrett, L. K., Hackman, R. C., Love, M. S., McNamara, C. W., Shaughnessy, T. K., Kondratiuk, A., Kurnick, M., Banfor, P. N., ... Van Voorhis, W. C. (2017). Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis. International Journal for Parasitology, 47(12), 753-763. https://doi.org/10.1016/j.ijpara.2017.08.006