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SCYX-7158, an Orally-Active Benzoxaborole for the Treatment of Stage 2 Human African Trypanosomiasis

By Robert T. Jacobs, Bakela Nare, Stephen A. Wring, Matthew D. Orr, Daitao Chen, Jessica M. Sligar, Matthew X. Jenks, Robert A. Noe, Tana S. Bowling, Luke T. Mercer, Cindy Rewerts, Eric Gaukel, Jennifer Owens, Robin Parham, Ryan Randolph, Beth Beaudet, Cyrus J. Bacchi, Nigel Yarlett, Jacob J. Plattner, Yvonne Freund, Charles Ding, Tsutomu Akama, Y.-K. Zhang, Reto Brun, Marcel Kaiser, Ivan Scandale and Robert Don

Abstract

Human African trypanosomiasis (HAT) is caused by infection with the parasite Trypanosoma brucei and is an important public health problem in sub-Saharan Africa. New, safe, and effective drugs are urgently needed to treat HAT, particularly stage 2 disease where the parasite infects the brain. Existing therapies for HAT have poor safety profiles, difficult treatment regimens, limited effectiveness, and a high cost of goods. Through an integrated drug discovery project, we have discovered and optimized a novel class of boron-containing small molecules, benzoxaboroles, to deliver SCYX-7158, an orally active preclinical drug candidate. SCYX-7158 cured mice infected with T. brucei, both in the blood and in the brain. Extensive pharmacokinetic characterization of SCYX-7158 in rodents and non-human primates supports the potential of this drug candidate for progression to IND-enabling studies in advance of clinical trials for stage 2 HAT

Topics: Research Article
Publisher: Public Library of Science
OAI identifier: oai:pubmedcentral.nih.gov:3125149
Provided by: PubMed Central

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