ArticleJournal of medicinal chemistry2017
Development of a Potent Inhibitor of the Plasmodium Proteasome with Reduced Mammalian Toxicity.
Article in Journal of medicinal chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 96 citations in OpenAlex.
- Ubiquitin-proteasome system inFrontiers in medicine · 2024Pooled it
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- Trichomonas vaginalis Drug Targets and Their Role in Drug Discovery and Development.Pharmaceutical research · 2026Review
- Inhibitors of the 20S proteasome β5 subunit as potent and selective agents againstAntimicrobial agents and chemotherapy · 2025Article
- Optimization of Species-Selective Reversible Proteasome Inhibitors for the Treatment of Malaria.Journal of medicinal chemistry · 2025Article
- A recombinant expression system for thebioRxiv : the preprint server for biology · 2025Article
- In Silico Design and Analysis of Cyanobacterial Pseudo Natural Products.Journal of natural products · 2025Article
- Enhancing schistosomiasis drug discovery approaches with optimized proteasome substrates.Protein science : a publication of the Protein Society · 2025Article
- Natural products as transmission-blocking agents against malaria: a comprehensive review of bioactive compounds and their therapeutic potential.Malaria journal · 2025Review
- Combating Malaria: Targeting the Ubiquitin-Proteasome System to Conquer Drug Resistance.Tropical medicine and infectious disease · 2025Review
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- Malaria parasite cysteine and aspartic proteases as key drug targets for antimalarial therapy.Journal of molecular modeling · 2025Review
- Structural comparison of human and Plasmodium proteasome β5 subunits: informing selective inhibitor design for anti-malaria agents.Malaria journal · 2025Article
- Carmaphycin B-Based Proteasome Inhibitors to Treat Human African Trypanosomiasis: Structure-Activity Relationship andACS infectious diseases · 2024Article
- Distinct substrate specificities of the three catalytic subunits of the Trichomonas vaginalis proteasome.Protein science : a publication of the Protein Society · 2024Article
- Evaluating Antimalarial Proteasome Inhibitors for Efficacy inACS omega · 2024Article
- Marine Cyanobacteria: A Rich Source of Structurally Unique Anti-Infectives for Drug Development.Molecules (Basel, Switzerland) · 2024Review
- Identification of Malaria-Selective Proteasome β5 Inhibitors Through Pharmacophore Modeling, Molecular Docking, and Molecular Dynamics Simulation.International journal of molecular sciences · 2024Article
- Structural elucidation of recombinant Trichomonas vaginalis 20S proteasome bound to covalent inhibitors.Nature communications · 2024Article
- Article
5 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
17 authors at 3 institutions in 2 countries.
Funding
Abstract
Naturally derived chemical compounds are the foundation of much of our pharmacopeia, especially in antiproliferative and anti-infective drug classes. Here, we report that a naturally derived molecule called carmaphycin B is a potent inhibitor against both the asexual and sexual blood stages of malaria infection. Using a combination of in silico molecular docking and in vitro directed evolution in a well-characterized drug-sensitive yeast model, we determined that these compounds target the β5 subunit of the proteasome. These studies were validated using in vitro inhibition assays with proteasomes isolated from Plasmodium falciparum. As carmaphycin B is toxic to mammalian cells, we synthesized a series of chemical analogs that reduce host cell toxicity while maintaining blood-stage and gametocytocidal antimalarial activity and proteasome inhibition. This study describes a promising new class of antimalarial compound based on the carmaphycin B scaffold, as well as several chemical structural features that serve to enhance antimalarial specificity.
Indexed as
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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.