ArticlePLoS neglected tropical diseases2014
Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.
Article in PLoS neglected tropical diseases, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
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- Pharmacophore Identification and Structure-Activity Relationship Analysis of a Series of Substituted Azaindoles as Inhibitors ofJournal of medicinal chemistry · 2024Article
- Aminopyridines in the development of drug candidates against protozoan neglected tropical diseases.Future medicinal chemistry · 2024Review
- Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.Frontiers in microbiology · 2023Article
- Structure, function and druggability of the African trypanosome flagellum.Journal of cellular physiology · 2022Review
- Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis.Journal of medicinal chemistry · 2021Article
- Medicinal Chemistry Optimization of a Diaminopurine Chemotype: Toward a Lead forJournal of medicinal chemistry · 2020Article
- Structure-property studies of an imidazoquinoline chemotype with antitrypanosomal activity.RSC medicinal chemistry · 2020Article
- Hit-to-Lead Optimization of Benzoxazepinoindazoles As Human African Trypanosomiasis Therapeutics.Journal of medicinal chemistry · 2020Article
- Anti-Trypanosomal Proteasome Inhibitors Cure Hemolymphatic and Meningoencephalic Murine Infection Models of African Trypanosomiasis.Tropical medicine and infectious disease · 2020Article
- Selectivity and Physicochemical Optimization of Repurposed Pyrazolo[1,5-Journal of medicinal chemistry · 2020Article
- Evaluation of a class of isatinoids identified from a high-throughput screen of human kinase inhibitors as anti-Sleeping Sickness agents.PLoS neglected tropical diseases · 2019Article
- High Throughput and Computational Repurposing for Neglected Diseases.Pharmaceutical research · 2018Review
- Series of Alkynyl-Substituted Thienopyrimidines as Inhibitors of Protozoan Parasite Proliferation.ACS medicinal chemistry letters · 2018Article
- The Importance of Collaboration between Industry, Academics, and Nonprofits in Tropical Disease Drug Discovery.ACS infectious diseases · 2018Article
- Optimization of physicochemical properties for 4-anilinoquinazoline inhibitors of trypanosome proliferation.European journal of medicinal chemistry · 2017Article
- Comprehensive data on a 2D-QSAR model for Heme Oxygenase isoform 1 inhibitors.Data in brief · 2017Article
- Sigma-1 and Sigma-2 receptor ligands induce apoptosis and autophagy but have opposite effect on cell proliferation in uveal melanoma.Oncotarget · 2017Article
- Novel lead compounds in pre-clinical development against African sleeping sickness.MedChemComm · 2017Review
- Novel 1,2-dihydroquinazolin-2-ones: Design, synthesis, and biological evaluation against Trypanosoma brucei.Bioorganic & medicinal chemistry letters · 2017Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.
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Registered trials
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