ArticleCell chemical biology2023
Dual-pharmacophore artezomibs hijack the Plasmodium ubiquitin-proteasome system to kill malaria parasites while overcoming drug resistance.
Article in Cell chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
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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.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Structure-Activity Relationship Study of Antimalarial Asparagine-Derived Proteasome Inhibitors.ACS omega · 2026Article
- Intracellular Activation of Dual-Pharmacophore Artezomib Enhances Selective Cytotoxicity in Hematologic Malignancies.Journal of medicinal chemistry · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Protective role ofFrontiers in pharmacology · 2026Article
- Protein degradation-based anti-infective drug research.Acta pharmaceutica Sinica. B · 2025Article
- Unlocking the antimalarial potential of novel steroid-tetraoxane hybrids through consensus molecular docking and molecular dynamics investigation.Scientific reports · 2025Article
- Towards next-generation treatment options to combat Plasmodium falciparum malaria.Nature reviews. Microbiology · 2025Review
- The essential genome ofScience (New York, N.Y.) · 2025Article
- Advances in WRKY regulation of immune responses in medicinal plants.Frontiers in plant science · 2025Review
- Characterization of antimalarial activity of artemisinin-based hybrid drugs.Antimicrobial agents and chemotherapy · 2024Article
- Structures revealing mechanisms of resistance and collateral sensitivity of Plasmodium falciparum to proteasome inhibitors.Nature communications · 2023Article
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Authors and funding
22 authors at 7 institutions in 3 countries.
Funding
Abstract
Artemisinins (ART) are critical anti-malarials and despite their use in combination therapy, ART-resistant Plasmodium falciparum is spreading globally. To counter ART resistance, we designed artezomibs (ATZs), molecules that link an ART with a proteasome inhibitor (PI) via a non-labile amide bond and hijack parasite's own ubiquitin-proteasome system to create novel anti-malarials in situ. Upon activation of the ART moiety, ATZs covalently attach to and damage multiple parasite proteins, marking them for proteasomal degradation. When damaged proteins enter the proteasome, their attached PIs inhibit protease function, potentiating the parasiticidal action of ART and overcoming ART resistance. Binding of the PI moiety to the proteasome active site is enhanced by distal interactions of the extended attached peptides, providing a mechanism to overcome PI resistance. ATZs have an extra mode of action beyond that of each component, thereby overcoming resistance to both components, while avoiding transient monotherapy seen when individual agents have disparate pharmacokinetic profiles.
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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.