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Bumped Kinase Inhibitors as therapy for apicomplexan parasitic diseases: lessons learned

Ryan Choi,Matthew A. Hulverson,Wenlin Huang,Rama S.R. Vidadala,Grant R. Whitman,Lynn K. Barrett,Deborah A. Schaefer,Dana P. Betzer,Michael W. Riggs,J. Stone Doggett,Andrew Hemphill,Luis Miguel Ortega-Mora,Molly C. McCloskey,Samuel L.M. Arnold,Robert C. Hackman,Kennan C. Marsh,James J. Lynch,Gail M. Freiberg,Bruce E. Leroy,Dale J. Kempf

International Journal for Parasitology（2020）

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Abstract
•BKIs that target CDPK1 in apicomplexan parasites with a glycine gatekeeper are promising new therapeutics.•Numerous challenges have shaped our selection of pre-clinical BKI candidates.•These include chirality, hERG, teratogenicity, cardiovascular, GI, and toxicity issues, and poor efficacy due to PK/PD.
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Key words
Apicomplexa,Bumped Kinase Inhibitor,Calcium-dependent Protein Kinases,Gatekeeper,Cryptosporidium,Toxoplasma,Neospora,Sarcocystis
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