ArticleScientific reports2015
New compound sets identified from high throughput phenotypic screening against three kinetoplastid parasites: an open resource.
Article in Scientific reports, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 145 papers.
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Who cites it
145 citing papers in PubMed.
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- In Vivo Efficacy and Biochemical Target Engagement of a Chromene-Based Inhibitor of Trypanosoma cruzi Lysyl-tRNA Synthetase.Journal of medicinal chemistry · 2026Article
- Prioritization of chemical scaffolds using the TDR Targets database: An integrative workflow for Trypanosoma cruzi drug discovery.PLoS neglected tropical diseases · 2026Article
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- Triazole-Functionalized Jatrophone Derivatives as Antiprotozoal Agents AgainstPharmaceuticals (Basel, Switzerland) · 2026Article
- Nucleoside Analogue with Thymidine Nucleobase InhibitsACS omega · 2026Article
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- 2-Aminothiophene Derivative SB-83 Inhibits Trypanothione Reductase and Modulates Cytokine Production inPathogens (Basel, Switzerland) · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Pathogenic Significance of Trypanosomatids: Progress in Drug Resistance, Control Strategies, and Artificial Intelligence.Interdisciplinary perspectives on infectious diseases · 2026Review
- Potent kinase inhibitors from the Merck KGaA OGHL: Novel hits against Trypanosoma brucei with potential for repurposing.PLoS neglected tropical diseases · 2025Article
- Structure-activity relationships of 1,5-dihydro-2RSC medicinal chemistry · 2025Article
- Hit-to-Lead Studies of Pyrazinylpiperazines against Visceral Leishmaniasis: Pharmacokinetic Profile andACS pharmacology & translational science · 2025Article
- High-throughput screening identifies novel chemical scaffolds targeting Leishmania donovani parasites.World journal of microbiology & biotechnology · 2025Article
- Transforming the chemotherapy of human African trypanosomiasis.Clinical microbiology reviews · 2025Review
- Inhibition of L-threonine dehydrogenase from Trypanosoma cruzi reduces glycine and acetate production and interferes with parasite growth and viability.The Journal of biological chemistry · 2025Article
- Efficacy of sulfonamides targeting malic enzyme in an animal model of Chagas disease.Frontiers in pharmacology · 2025Article
- Reporter genes and transgenicFrontiers in medicine · 2025Review
85 more citing papers are in PubMed but not listed here.
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21 authors.
Funding
Abstract
Using whole-cell phenotypic assays, the GlaxoSmithKline high-throughput screening (HTS) diversity set of 1.8 million compounds was screened against the three kinetoplastids most relevant to human disease, i.e. Leishmania donovani, Trypanosoma cruzi and Trypanosoma brucei. Secondary confirmatory and orthogonal intracellular anti-parasiticidal assays were conducted, and the potential for non-specific cytotoxicity determined. Hit compounds were chemically clustered and triaged for desirable physicochemical properties. The hypothetical biological target space covered by these diversity sets was investigated through bioinformatics methodologies. Consequently, three anti-kinetoplastid chemical boxes of ~200 compounds each were assembled. Functional analyses of these compounds suggest a wide array of potential modes of action against kinetoplastid kinases, proteases and cytochromes as well as potential host-pathogen targets. This is the first published parallel high throughput screening of a pharma compound collection against kinetoplastids. The compound sets are provided as an open resource for future lead discovery programs, and to address important research questions.
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