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. Lynch & 6 others Gail M. Freiberg, Dale J. Kempf, Dustin J. Maly, Michael W. Riggs, Kayode K. Ojo, Wesley C. Van Voorhis

Research output: Research - peer-reviewArticle

  • 1 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.

LanguageEnglish (US)
JournalInternational Journal for Parasitology
DOIs
StateAccepted/In press - 2017

Fingerprint

Cryptosporidiosis
Phosphotransferases
Therapeutics
Safety
Lead
Cardiotoxicity

Keywords

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

ASJC Scopus subject areas

  • Parasitology
  • Infectious Diseases

Cite this

Hulverson, M. A., Choi, R., Arnold, S. L. M., Schaefer, D. A., Hemphill, A., McCloskey, M. C., ... Van Voorhis, W. C. (2017). Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis. International Journal for Parasitology. DOI: 10.1016/j.ijpara.2017.08.006

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

In: International Journal for Parasitology, 2017.

Research output: Research - peer-reviewArticle

Hulverson, MA, Choi, R, Arnold, SLM, Schaefer, DA, Hemphill, A, McCloskey, MC, Betzer, DP, Müller, J, Vidadala, RSR, Whitman, GR, Rivas, KL, Barrett, LK, Hackman, RC, Love, MS, McNamara, CW, Shaughnessy, TK, Kondratiuk, A, Kurnick, M, Banfor, PN, Lynch, JJ, Freiberg, GM, Kempf, DJ, Maly, DJ, Riggs, MW, Ojo, KK & Van Voorhis, WC 2017, 'Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis' International Journal for Parasitology. DOI: 10.1016/j.ijpara.2017.08.006
Hulverson MA, Choi R, Arnold SLM, Schaefer DA, Hemphill A, McCloskey MC et al. Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis. International Journal for Parasitology. 2017. Available from, DOI: 10.1016/j.ijpara.2017.08.006
Hulverson, Matthew A. ; Choi, Ryan ; Arnold, Samuel L.M. ; Schaefer, Deborah A. ; Hemphill, Andrew ; McCloskey, Molly C. ; Betzer, Dana P. ; Müller, Joachim ; Vidadala, Rama S.R. ; Whitman, Grant R. ; Rivas, Kasey L. ; Barrett, Lynn K. ; Hackman, Robert C. ; Love, Melissa S. ; McNamara, Case W. ; Shaughnessy, Thomas K. ; Kondratiuk, Alison ; Kurnick, Matthew ; Banfor, Patricia N. ; Lynch, James J. ; Freiberg, Gail M. ; Kempf, Dale J. ; Maly, Dustin J. ; Riggs, Michael W. ; Ojo, Kayode K. ; Van Voorhis, Wesley C./ Advances in bumped kinase inhibitors for human and animal therapy for cryptosporidiosis. In: International Journal for Parasitology. 2017
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AU - Hemphill,Andrew

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AU - Betzer,Dana P.

AU - Müller,Joachim

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AU - Rivas,Kasey L.

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AU - Love,Melissa S.

AU - McNamara,Case W.

AU - Shaughnessy,Thomas K.

AU - Kondratiuk,Alison

AU - Kurnick,Matthew

AU - Banfor,Patricia N.

AU - Lynch,James J.

AU - Freiberg,Gail M.

AU - Kempf,Dale J.

AU - Maly,Dustin J.

AU - Riggs,Michael W.

AU - Ojo,Kayode K.

AU - Van Voorhis,Wesley C.

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