ArticleBioorganic & medicinal chemistry letters2019
HSP60/10 chaperonin systems are inhibited by a variety of approved drugs, natural products, and known bioactive molecules.
Article in Bioorganic & medicinal chemistry letters, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 35 citations in OpenAlex.
- Exploring Novel Antibiotics by Targeting the GroEL/GroES Chaperonin System.ACS pharmacology & translational science · 2025Review
- Discovery of a Tunable Heterocyclic Electrophile 4-Chloro-pyrazolopyridine That Defines a Unique Subset of Ligandable Cysteines.ACS chemical biology · 2024Article
- Review
- Transcriptome Analysis ofInternational journal of environmental research and public health · 2022Article
- Bis-aryl-α,β-unsaturated ketone (ABK) chaperonin inhibitors exhibit selective cytotoxicity to colorectal cancer cells that correlates with levels of aberrant HSP60 in the cytosol.Bioorganic & medicinal chemistry · 2022Article
- Extraction and Visualization of Protein Aggregates after Treatment of Escherichia coli with a Proteotoxic Stressor.Journal of visualized experiments : JoVE · 2021Article
- Exploiting the HSP60/10 chaperonin system as a chemotherapeutic target for colorectal cancer.Bioorganic & medicinal chemistry · 2021Article
- Potential therapeutic targets shared between leishmaniasis and cancer.Parasitology · 2021Review
- Repurposing old drugs as new inhibitors of the ubiquitin-proteasome pathway for cancer treatment.Seminars in cancer biology · 2021Review
- Bacterial Protein Homeostasis Disruption as a Therapeutic Intervention.Frontiers in molecular biosciences · 2021Review
- Analogs of nitrofuran antibiotics are potent GroEL/ES inhibitor pro-drugs.Bioorganic & medicinal chemistry · 2020Article
- Addition of ethylamines to the phenols of bithionol and synthetic retinoids does not elicit activity in gram-negative bacteria.Bioorganic & medicinal chemistry letters · 2020Article
- 100 Years of Suramin.Antimicrobial agents and chemotherapy · 2020Review
- Hsp60 Post-translational Modifications: Functional and Pathological Consequences.Frontiers in molecular biosciences · 2020Review
- Small Molecule Inhibitors Targeting the Heat Shock Protein System of Human Obligate Protozoan Parasites.International journal of molecular sciences · 2019Review
- Dual-targeting GroEL/ES chaperonin and protein tyrosine phosphatase B (PtpB) inhibitors: A polypharmacology strategy for treating Mycobacterium tuberculosis infections.Bioorganic & medicinal chemistry letters · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
All living organisms contain a unique class of molecular chaperones called 60 kDa heat shock proteins (HSP60 - also known as GroEL in bacteria). While some organisms contain more than one HSP60 or GroEL isoform, at least one isoform has always proven to be essential. Because of this, we have been investigating targeting HSP60 and GroEL chaperonin systems as an antibiotic strategy. Our initial studies focused on applying this antibiotic strategy for treating African sleeping sickness (caused by Trypanosoma brucei parasites) and drug-resistant bacterial infections (in particular Methicillin-resistant Staphylococcus aureus - MRSA). Intriguingly, during our studies we found that three known antibiotics - suramin, closantel, and rafoxanide - were potent inhibitors of bacterial GroEL and human HSP60 chaperonin systems. These findings prompted us to explore what other approved drugs, natural products, and known bioactive molecules might also inhibit HSP60 and GroEL chaperonin systems. Initial high-throughput screening of 3680 approved drugs, natural products, and known bioactives identified 161 hit inhibitors of the Escherichia coli GroEL chaperonin system (4.3% hit rate). From a purchased subset of 60 hits, 29 compounds (48%) re-confirmed as selective GroEL inhibitors in our assays, all of which were nearly equipotent against human HSP60. These findings illuminate the notion that targeting chaperonin systems might be a more common occurrence than we previously appreciated. Future studies are needed to determine if the in vivo modes of action of these approved drugs, natural products, and known bioactive molecules are related to GroEL and HSP60 inhibition.
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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.