Comparison of Toxicities among Different Bumped Kinase Inhibitor Analogs for Treatment of Cryptosporidiosis

Author:

Hulverson Matthew A.1ORCID,Choi Ryan1,Schaefer Deborah A.2,Betzer Dana P.2,McCloskey Molly C.1,Whitman Grant R.1ORCID,Huang Wenlin3,Lee Sangun4ORCID,Pranata Andy5,McLeod Malcolm D.5,Marsh Kennan C.6,Kempf Dale J.67,LeRoy Bruce E.6,Zafiratos Mark T.6,Bielinski Aimee L.6,Hackman Robert C.8910,Ojo Kayode K.1,Arnold Samuel L. M.1ORCID,Barrett Lynn K.1,Tzipori Saul4,Riggs Michael W.2,Fan Erkang3,Van Voorhis Wesley C.1ORCID

Affiliation:

1. Department of Medicine, Division of Allergy and Infectious Disease, Center for Emerging and Reemerging Infectious Disease (CERID), University of Washington, Seattle, Washington, USA

2. School of Animal and Comparative Biomedical Sciences, College of Agriculture and Life Sciences, University of Arizona, Tucson, Arizona, USA

3. Department of Biochemistry, University of Washington, Seattle, Washington, USA

4. Department of Infectious Disease and Global Health, Cummings School of Veterinary Medicine at Tufts University, North Grafton, Massachusetts, USA

5. Research School of Chemistry, Australian National University, Canberra, ACT, Australia

6. Research and Development, AbbVie, Inc., North Chicago, Illinois, USA

7. Former employee of AbbVie, Inc., North Chicago, Illinois, USA

8. Fred Hutchinson Cancer Research Center, Seattle, Washington, USA

9. Department of Pathology, University of Washington, Seattle, Washington, USA

10. Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA

Abstract

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.

Funder

HHS | NIH | National Institute of Allergy and Infectious Diseases

U.S. Department of Agriculture

Bill and Melinda Gates Foundation

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Cited by 2 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

1. Treating cryptosporidiosis: A review on drug discovery strategies;International Journal for Parasitology: Drugs and Drug Resistance;2024-08

2. In vitro screening technologies for the discovery and development of novel drugs against Toxoplasma gondii;Expert Opinion on Drug Discovery;2023-11-03

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