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Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis

Author

Listed:
  • Christopher S. Lunde

    (Anacor Pharmaceuticals)

  • Erin E. Stebbins

    (University of Vermont Robert R. Larner College of Medicine)

  • Rajiv S. Jumani

    (University of Vermont Robert R. Larner College of Medicine
    University of Vermont College of Agriculture and Life Sciences)

  • Md Mahmudul Hasan

    (University of Vermont Robert R. Larner College of Medicine
    University of Vermont College of Agriculture and Life Sciences)

  • Peter Miller

    (University of Vermont Robert R. Larner College of Medicine)

  • John Barlow

    (University of Vermont College of Agriculture and Life Sciences)

  • Yvonne R. Freund

    (Anacor Pharmaceuticals)

  • Pamela Berry

    (Anacor Pharmaceuticals)

  • Rianna Stefanakis

    (Anacor Pharmaceuticals)

  • Jiri Gut

    (University of California San Francisco)

  • Philip J. Rosenthal

    (University of California San Francisco)

  • Melissa S. Love

    (Calibr at Scripps Research)

  • Case W. McNamara

    (Calibr at Scripps Research)

  • Eric Easom

    (Anacor Pharmaceuticals)

  • Jacob J. Plattner

    (Anacor Pharmaceuticals)

  • Robert T. Jacobs

    (Anacor Pharmaceuticals)

  • Christopher D. Huston

    (University of Vermont Robert R. Larner College of Medicine
    University of Vermont College of Agriculture and Life Sciences)

Abstract

Cryptosporidiosis is a leading cause of life-threatening diarrhea in young children and causes chronic diarrhea in AIDS patients, but the only approved treatment is ineffective in malnourished children and immunocompromised people. We here use a drug repositioning strategy and identify a promising anticryptosporidial drug candidate. Screening a library of benzoxaboroles comprised of analogs to four antiprotozoal chemical scaffolds under pre-clinical development for neglected tropical diseases for Cryptosporidium growth inhibitors identifies the 6-carboxamide benzoxaborole AN7973. AN7973 blocks intracellular parasite development, appears to be parasiticidal, and potently inhibits the two Cryptosporidium species most relevant to human health, C. parvum and C. hominis. It is efficacious in murine models of both acute and established infection, and in a neonatal dairy calf model of cryptosporidiosis. AN7973 also possesses favorable safety, stability, and PK parameters, and therefore, is an exciting drug candidate for treating cryptosporidiosis.

Suggested Citation

  • Christopher S. Lunde & Erin E. Stebbins & Rajiv S. Jumani & Md Mahmudul Hasan & Peter Miller & John Barlow & Yvonne R. Freund & Pamela Berry & Rianna Stefanakis & Jiri Gut & Philip J. Rosenthal & Meli, 2019. "Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10687-y
    DOI: 10.1038/s41467-019-10687-y
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    Cited by:

    1. Jubilee Ajiboye & José E. Teixeira & Makafui Gasonoo & Ethan B. Mattice & Bethany Korwin-Mihavics & Peter Miller & Alexandra C. Cameron & Erin Stebbins & Scott D. Campbell & David W. Griggs & Thomas S, 2024. "Identification of potent and orally efficacious phosphodiesterase inhibitors in Cryptosporidium parvum-infected immunocompromised male mice," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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