ArticleCell communication and signaling : CCS2024
Chemoproteomics-based profiling reveals potential antimalarial mechanism of Celastrol by disrupting spermidine and protein synthesis.
Article in Cell communication and signaling : CCS, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 11 citations in OpenAlex.
- Chemoproteomic Identification of AKT2 as a Paclitaxel-Binding Protein via C─C Bond-Linked Probe PTX-4 in Paclitaxel-Resistant Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting protein-protein interactions in Plasmodium: from asexual replication to sexual development.Parasites & vectors · 2026Review
- Natural Product-Derived Activity-Based and Affinity-Based Probes: Tools for Mechanism of Action Studies.Molecules (Basel, Switzerland) · 2026Review
- Emerging Target Discovery Strategies Drive the Decoding of Therapeutic Power of Natural Products and Further Drug Development: A Case Study of Celastrol.Exploration (Beijing, China) · 2025Review
- Evaluating Biocompatibility: From Classical Techniques to State-of-the-Art Functional Proteomics.Nanomaterials (Basel, Switzerland) · 2025Review
- Celastrol targets CKB-mediated futile creatine cycle in human brown adipocytes thermogenesis.Metabolism open · 2025Article
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14 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundMalaria remains a global health burden, and the emergence and increasing spread of drug resistance to current antimalarials poses a major challenge to malaria control. There is an urgent need to find new drugs or strategies to alleviate this predicament. Celastrol (Cel) is an extensively studied natural bioactive compound that has shown potentially promising antimalarial activity, but its antimalarial mechanism remains largely elusive.
methodsWe first established the Plasmodium berghei ANKA-infected C57BL/6 mouse model and systematically evaluated the antimalarial effects of Cel in conjunction with in vitro culture of Plasmodium falciparum. The potential antimalarial targets of Cel were then identified using a Cel activity probe based on the activity-based protein profiling (ABPP) technology. Subsequently, the antimalarial mechanism was analyzed by integrating with proteomics and transcriptomics. The binding of Cel to the identified key target proteins was verified by a series of biochemical experiments and functional assays.
resultsThe results of the pharmacodynamic assay showed that Cel has favorable antimalarial activity both in vivo and in vitro. The ABPP-based target profiling showed that Cel can bind to a number of proteins in the parasite. Among the 31 identified potential target proteins of Cel, PfSpdsyn and PfEGF1-α were verified to be two critical target proteins, suggesting the role of Cel in interfering with the de novo synthesis of spermidine and proteins of the parasite, thus exerting its antimalarial effects.
conclusionsIn conclusion, this study reports for the first time the potential antimalarial targets and mechanism of action of Cel using the ABPP strategy. Our work not only support the expansion of Cel as a potential antimalarial agent or adjuvant, but also establishes the necessary theoretical basis for the development of potential antimalarial drugs with pentacyclic triterpenoid structures, as represented by Cel. Video Abstract.
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