2. Academic Validation
  3. Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis

Identification of a potent benzoxaborole drug candidate for treating cryptosporidiosis

  • Nat Commun. 2019 Jun 27;10(1):2816. doi: 10.1038/s41467-019-10687-y.
Christopher S Lunde 1,  Erin E Stebbins 2,  Rajiv S Jumani 2 3,  Md Mahmudul Hasan 2 3,  Peter Miller 2,  John Barlow 4,  Yvonne R Freund 1,  Pamela Berry 1,  Rianna Stefanakis 1,  Jiri Gut 5,  Philip J Rosenthal 5,  Melissa S Love 6,  Case W McNamara 6,  Eric Easom 1,  Jacob J Plattner 1,  Robert T Jacobs 1,  Christopher D Huston 7 8
Affiliations

Affiliations

  • 1 Anacor Pharmaceuticals, Palo Alto, CA, 4230, USA.
  • 2 Department of Medicine, University of Vermont Robert R. Larner College of Medicine, Burlington, VT, 05405, USA.
  • 3 Department of Microbiology and Molecular Genetics, University of Vermont College of Agriculture and Life Sciences, Burlington, VT, 05405, USA.
  • 4 Department of Animal and Veterinary Sciences, University of Vermont College of Agriculture and Life Sciences, Burlington, VT, 05405, USA.
  • 5 Department of Medicine, University of California San Francisco, San Francisco, CA, 94143, USA.
  • 6 Calibr at Scripps Research, La Jolla, CA, 92037, USA.
  • 7 Department of Medicine, University of Vermont Robert R. Larner College of Medicine, Burlington, VT, 05405, USA. [email protected].
  • 8 Department of Microbiology and Molecular Genetics, University of Vermont College of Agriculture and Life Sciences, Burlington, VT, 05405, USA. [email protected].
PMID: 31249291 DOI: 10.1038/s41467-019-10687-y
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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-128337
    99.37%, Parasite Inhibitor