ArticlePLoS neglected tropical diseases2015
Genomic and Proteomic Studies on the Mode of Action of Oxaboroles against the African Trypanosome.
Article in PLoS neglected tropical diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- Chemotherapy for second-stage human African trypanosomiasis: drugs in use.The Cochrane database of systematic reviews · 2021Pooled it
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Targeting Cysteine Proteases and their Inhibitors to Combat Trypanosomiasis.Current medicinal chemistry · 2024Review
- The critical role of mode of action studies in kinetoplastid drug discovery.Frontiers in drug discovery · 2023Article
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- Transcriptional differentiation of Trypanosoma brucei during in vitro acquisition of resistance to acoziborole.PLoS neglected tropical diseases · 2021Article
- How Physiologic Targets Can Be Distinguished from Drug-Binding Proteins.Molecular pharmacology · 2021Article
- Identification of Resistance Determinants for a Promising Antileishmanial Oxaborole Series.Microorganisms · 2021Article
- Veterinary trypanocidal benzoxaboroles are peptidase-activated prodrugs.PLoS pathogens · 2020Article
- Experimental Strategies to Explore Drug Action and Resistance in Kinetoplastid Parasites.Microorganisms · 2020Review
- Defeating the trypanosomatid trio: proteomics of the protozoan parasites causing neglected tropical diseases.RSC medicinal chemistry · 2020Review
- New Drugs for Human African Trypanosomiasis: A Twenty First Century Success Story.Tropical medicine and infectious disease · 2020Review
- Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- The trypanocidal benzoxaborole AN7973 inhibits trypanosome mRNA processing.PLoS pathogens · 2018Article
- Benzoxaborole treatment perturbs S-adenosyl-L-methionine metabolism in Trypanosoma brucei.PLoS neglected tropical diseases · 2018Article
- An automated high-throughput system for phenotypic screening of chemical libraries on C. elegans and parasitic nematodes.International journal for parasitology. Drugs and drug resistance · 2018Article
- Host-parasite co-metabolic activation of antitrypanosomal aminomethyl-benzoxaboroles.PLoS pathogens · 2018Article
- Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need.Nature reviews. Microbiology · 2017Review
- Rapid Chagas Disease Drug Target Discovery Using Directed Evolution in Drug-Sensitive Yeast.ACS chemical biology · 2017Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
SCYX-7158, an oxaborole, is currently in Phase I clinical trials for the treatment of human African trypanosomiasis. Here we investigate possible modes of action against Trypanosoma brucei using orthogonal chemo-proteomic and genomic approaches. SILAC-based proteomic studies using an oxaborole analogue immobilised onto a resin was used either in competition with a soluble oxaborole or an immobilised inactive control to identify thirteen proteins common to both strategies. Cell-cycle analysis of cells incubated with sub-lethal concentrations of an oxaborole identified a subtle but significant accumulation of G2 and >G2 cells. Given the possibility of compromised DNA fidelity, we investigated long-term exposure of T. brucei to oxaboroles by generating resistant cell lines in vitro. Resistance proved more difficult to generate than for drugs currently used in the field, and in one of our three cell lines was unstable. Whole-genome sequencing of the resistant cell lines revealed single nucleotide polymorphisms in 66 genes and several large-scale genomic aberrations. The absence of a simple consistent mechanism among resistant cell lines and the diverse list of binding partners from the proteomic studies suggest a degree of polypharmacology that should reduce the risk of resistance to this compound class emerging in the field. The combined genetic and chemical biology approaches have provided lists of candidates to be investigated for more detailed information on the mode of action of this promising new drug class.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.