Matthew A Hulverson, Ryan Choi, Deborah A Schaefer, Dana P Betzer, Molly C McCloskey, Grant R Whitman, Wenlin Huang, Sangun Lee, Andy Pranata, Malcolm D McLeod, Kennan C Marsh, Dale J Kempf, Bruce E LeRoy, Mark T Zafiratos, Aimee L Bielinski, Robert C Hackman, Kayode K Ojo, Samuel L M Arnold, Lynn K Barrett, Saul Tzipori, Michael W Riggs, Erkang Fan, Wesley C Van Voorhis
Recent advances on the development of bumped kinase inhibitors for treatment of cryptosporidiosis have focused on the 5-aminopyrazole-4-carboxamide scaffold, due to analogs that have less hERG inhibition, superior efficacy, and strong in vitro safety profiles. Three compounds, BKI-1770, -1841, and -1708, showed strong efficacy in C. parvum infected mice. Both BKI-1770 and BKI-1841 had efficacy in the C. parvum newborn calf model, reducing diarrhea and oocyst excretion. However, both compounds caused hyperflexion of the limbs seen as dropped pasterns...
March 15, 2023: Antimicrobial Agents and Chemotherapy