ArticleNature2016
Proteasome inhibition for treatment of leishmaniasis, Chagas disease and sleeping sickness.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 209 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
209 citing papers in PubMed, 1 synthesis or guideline pooled it, 408 citations in OpenAlex.
- Using meta-analysis and machine learning to investigate the transcriptional response of immune cells to Leishmania infection.PLoS neglected tropical diseases · 2024Pooled it
- Safety and pharmacokinetics of GSK3494245, a highly selective Leishmaniasis kinetoplastid proteasome inhibitor for the treatment of visceral leishmaniasis: A Phase 1, randomized, single ascending dose escalation study in healthy participants.PLoS neglected tropical diseases · 2026Trial
- Article
- IID432, a parasite-selective topoisomerase II inhibitor, achieves rapid single-dose parasite clearance in a murine chronic Chagas model.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Five-layer systems analysis ofeLife · 2026Article
- Integrating Molecular Similarity and AlphaFold-Based Structural Alignment for Target Discovery inPharmaceuticals (Basel, Switzerland) · 2026Article
- Anticancer proteasome inhibitors are detrimental to the growth of Toxoplasma gondii in vitro.BMC research notes · 2026Article
- Revisiting cysteine protease function inMicrobiology spectrum · 2026Article
- Trichomonas vaginalis Drug Targets and Their Role in Drug Discovery and Development.Pharmaceutical research · 2026Review
- Chemical genetics reveals Leishmania KKT2 and CRK9 kinase activity is required for cell cycle progression.PLoS pathogens · 2026Article
- Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination.npj antimicrobials and resistance · 2026Article
- FMOPhore for hotspot identification and efficient fragment-to-lead growth strategies.Nature communications · 2026Article
- ExploringAntimicrobial agents and chemotherapy · 2026Article
- Decoding efficacy and resistance space at a drug binding site.Nature communications · 2026Article
- Parasitic diseases in heart transplantation: challenges of Toxoplasmosis and Chagas Disease.JHLT open · 2026Review
- Discovery of IID432 for Chagas Disease: A Cyanotriazole Inhibitor ofJournal of medicinal chemistry · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- Old drugs, new weapons: current trends in repurposing therapies against antimicrobial resistance.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2026Review
- Trypanosomatid parasites, translational research in a One Health, One World environment.Frontiers in chemistry · 2026Review
- Inhibitors of the 20S proteasome β5 subunit as potent and selective agents againstAntimicrobial agents and chemotherapy · 2025Article
149 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
35 authors at 4 institutions in 3 countries.
Funding
Abstract
Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide and lead to more than 50,000 deaths annually. The diseases are caused by infection with the kinetoplastid parasites Trypanosoma cruzi, Leishmania spp. and Trypanosoma brucei spp., respectively. These parasites have similar biology and genomic sequence, suggesting that all three diseases could be cured with drugs that modulate the activity of a conserved parasite target. However, no such molecular targets or broad spectrum drugs have been identified to date. Here we describe a selective inhibitor of the kinetoplastid proteasome (GNF6702) with unprecedented in vivo efficacy, which cleared parasites from mice in all three models of infection. GNF6702 inhibits the kinetoplastid proteasome through a non-competitive mechanism, does not inhibit the mammalian proteasome or growth of mammalian cells, and is well-tolerated in mice. Our data provide genetic and chemical validation of the parasite proteasome as a promising therapeutic target for treatment of kinetoplastid infections, and underscore the possibility of developing a single class of drugs for these neglected diseases.
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What OpenQuestion holds
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.