ArticleNature communications2021
Fast acting allosteric phosphofructokinase inhibitors block trypanosome glycolysis and cure acute African trypanosomiasis in mice.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 42 citations in OpenAlex.
- A covalent PFKL activator suppresses tumor growth.Nature chemical biology · 2026Article
- Profile of lysine acetylation in Eimeria tenella and its potential implications for anticoccidial research.Parasites & vectors · 2026Article
- Advances and challenges in the search for new treatments for Chagas disease.Memorias do Instituto Oswaldo Cruz · 2026Review
- A Covalent PFKL Activator Suppresses Tumor Growth.bioRxiv : the preprint server for biology · 2025Article
- Discovery of Novel CRK12 Inhibitors for the Treatment of Human African Trypanosomiasis: An Integrated Computational and Experimental Approach.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The more we learn, the more diverse it gets: structures, functions and evolution in the Phosphofructokinase Superfamily.The Biochemical journal · 2025Review
- Allosteric inhibition of trypanosomatid pyruvate kinases by a camelid single-domain antibody.eLife · 2025Article
- MAGPIE: An interactive tool for visualizing and analyzing protein-ligand interactions.Protein science : a publication of the Protein Society · 2024Article
- Article
- The bloodstream form of Trypanosoma brucei displays non-canonical gluconeogenesis.PLoS neglected tropical diseases · 2024Article
- PEX1 is essential for glycosome biogenesis and trypanosomatid parasite survival.Frontiers in cellular and infection microbiology · 2024Article
- In silico prediction of some pharmacokinetic, safety, biological activity and molecular docking studies of 1-piperazine indole hybrid with nicotinic amide and nicotinic acid and their analogues.SAGE open medicine · 2024Article
- Enolase Inhibitors as Early Lead Therapeutics againstPathogens (Basel, Switzerland) · 2023Article
- Protein kinases on carbon metabolism: potential targets for alternative chemotherapies against toxoplasmosis.Frontiers in cellular and infection microbiology · 2023Review
- Metabolic insights into phosphofructokinase inhibition in bloodstream-form trypanosomes.Frontiers in cellular and infection microbiology · 2023Article
- Therapeutic Targeting the Allosteric Cysteinome of RAS and Kinase Families.Journal of molecular biology · 2022Review
- Digalloyl Glycoside: A Potential Inhibitor of Trypanosomal PFK fromPlants (Basel, Switzerland) · 2022Article
- The History of Anti-Trypanosome Vaccine Development Shows That Highly Immunogenic and Exposed Pathogen-Derived Antigens Are Not Necessarily Good Target Candidates: Enolase and ISG75 as Examples.Pathogens (Basel, Switzerland) · 2021Article
- Novel Trypanocidal Inhibitors that Block Glycosome Biogenesis by Targeting PEX3-PEX19 Interaction.Frontiers in cell and developmental biology · 2021Article
Corrections and comments
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
The parasitic protist Trypanosoma brucei is the causative agent of Human African Trypanosomiasis, also known as sleeping sickness. The parasite enters the blood via the bite of the tsetse fly where it is wholly reliant on glycolysis for the production of ATP. Glycolytic enzymes have been regarded as challenging drug targets because of their highly conserved active sites and phosphorylated substrates. We describe the development of novel small molecule allosteric inhibitors of trypanosome phosphofructokinase (PFK) that block the glycolytic pathway resulting in very fast parasite kill times with no inhibition of human PFKs. The compounds cross the blood brain barrier and single day oral dosing cures parasitaemia in a stage 1 animal model of human African trypanosomiasis. This study demonstrates that it is possible to target glycolysis and additionally shows how differences in allosteric mechanisms may allow the development of species-specific inhibitors to tackle a range of proliferative or infectious diseases.
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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.