ArticleProceedings of the National Academy of Sciences of the United States of America2012
Discovery of antimicrobial ribonucleotide reductase inhibitors by screening in microwell format.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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
20 citing papers in PubMed, 27 citations in OpenAlex.
- Targeting PRMTs with small-molecule inhibitors: a comprehensive review.RSC medicinal chemistry · 2026Review
- Real-time assay of ribonucleotide reductase activity with a fluorescent RNA aptamer.FEBS letters · 2026Article
- Quercetin as a Promising Antiprotozoan Phytochemical: Current Knowledge and Future Research Avenues.BioMed research international · 2024Review
- Small Molecule Inhibition of an Exopolysaccharide Modification Enzyme is a Viable Strategy To Block Pseudomonas aeruginosa Pel Biofilm Formation.Microbiology spectrum · 2023Article
- Safety assessment ofFrontiers in microbiology · 2023Article
- Overview on Strategies and Assays for Antibiotic Discovery.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Inhibitors of the Cancer Target Ribonucleotide Reductase, Past and Present.Biomolecules · 2022Review
- Antisense inhibition of the Escherichia coli NrdAB aerobic ribonucleotide reductase is bactericidal due to induction of DNA strand breaks.The Journal of antimicrobial chemotherapy · 2021Article
- RNase I ModulatesACS chemical biology · 2020Article
- Article
- Subunit Interaction Dynamics of Class Ia Ribonucleotide Reductases: In Search of a Robust Assay.Biochemistry · 2020Article
- Compounds with capacity to quench the tyrosyl radical in Pseudomonas aeruginosa ribonucleotide reductase.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2019Article
- Novel ATP-cone-driven allosteric regulation of ribonucleotide reductase via the radical-generating subunit.eLife · 2018Article
- A ribonucleotide reductase inhibitor with deoxyribonucleoside-reversible cytotoxicity.Molecular oncology · 2016Article
- Diversity in Overall Activity Regulation of Ribonucleotide Reductase.The Journal of biological chemistry · 2015Article
- Novel immunosuppressive agent caerulomycin A exerts its effect by depleting cellular iron content.British journal of pharmacology · 2015Article
- Biochemical Characterization of the Split Class II Ribonucleotide Reductase from Pseudomonas aeruginosa.PloS one · 2015Article
- PubChem applications in drug discovery: a bibliometric analysis.Drug discovery today · 2014Review
- Phosphines are ribonucleotide reductase reductants that act via C-terminal cysteines similar to thioredoxins and glutaredoxins.Scientific reports · 2014Article
- Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription.Bioorganic & medicinal chemistry letters · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Ribonucleotide reductase (RNR) catalyzes reduction of the four different ribonucleotides to their corresponding deoxyribonucleotides and is the rate-limiting enzyme in DNA synthesis. RNR is a well-established target for the antiproliferative drugs Gemzar and Hydrea, for antisense therapy, and in combination chemotherapies. Surprisingly, few novel drugs that target RNR have emerged, partly because RNR activity assays are laboratory-intense and exclude high-throughput methodologies. Here, we present a previously undescribed PCR-based assay for RNR activity measurements in microplate format. We validated the approach by screening a diverse library of 1,364 compounds for inhibitors of class I RNR from the opportunistic pathogen Pseudomonas aeruginosa, and we identified 27 inhibitors with IC(50) values from ∼200 nM to 30 μM. Interestingly, a majority of the identified inhibitors have been found inactive in human cell lines as well as in anticancer and in vivo tumor tests as reported by the PubChem BioAssay database. Four of the RNR inhibitors inhibited growth of P. aeruginosa, and two were also found to affect the transcription of RNR genes and to decrease the cellular deoxyribonucleotide pools. This unique PCR-based assay works with any RNR enzyme and any substrate nucleotide, and thus opens the door to high-throughput screening for RNR inhibitors in drug discovery.
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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.