ArticleBioorganic & medicinal chemistry2019
Identification of a potent small-molecule inhibitor of bacterial DNA repair that potentiates quinolone antibiotic activity in methicillin-resistant Staphylococcus aureus.
Article in Bioorganic & medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The trial behind it
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Who cites it
14 citing papers in PubMed, 30 citations in OpenAlex.
- Small-molecule inhibitors block NorA efflux by conformational trapping.Nature chemical biology · 2026Article
- Synergistic Effects of IMP-1700, Ciprofloxacin, and X-Ray Radiation in Bacteria and Mammalian Cell Lines: Implications for Use in Antimicrobial-Resistant Bacteria.MicrobiologyOpen · 2026Article
- Base excision repair inFrontiers in microbiology · 2026Review
- Development of an inhibitor of the mutagenic SOS response that suppresses the evolution of quinolone antibiotic resistance.Chemical science · 2024Article
- Review
- Article
- Mechanistic insight into the repair of C8-linked pyrrolobenzodiazepine monomer-mediated DNA damage.RSC medicinal chemistry · 2022Article
- Iron Chelator DIBI Suppresses Formation of Ciprofloxacin-Induced Antibiotic Resistance inAntibiotics (Basel, Switzerland) · 2022Article
- Defects in DNA double-strand break repair resensitize antibiotic-resistant Escherichia coli to multiple bactericidal antibiotics.MicrobiologyOpen · 2022Article
- Alternative Treatment Strategies for Secondary Bacterial and Fungal Infections Associated with COVID-19.Infectious diseases and therapy · 2022Review
- Biological Effects of Quinolones: A Family of Broad-Spectrum Antimicrobial Agents.Molecules (Basel, Switzerland) · 2021Review
- RexAB Promotes the Survival of Staphylococcus aureus Exposed to Multiple Classes of Antibiotics.Antimicrobial agents and chemotherapy · 2021Article
- Article
- Multitarget Approaches against Multiresistant Superbugs.ACS infectious diseases · 2020Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
The global emergence of antibiotic resistance is one of the most serious challenges facing modern medicine. There is an urgent need for validation of new drug targets and the development of small molecules with novel mechanisms of action. We therefore sought to inhibit bacterial DNA repair mediated by the AddAB/RecBCD protein complexes as a means to sensitize bacteria to DNA damage caused by the host immune system or quinolone antibiotics. A rational, hypothesis-driven compound optimization identified IMP-1700 as a cell-active, nanomolar potency compound. IMP-1700 sensitized multidrug-resistant Staphylococcus aureus to the fluoroquinolone antibiotic ciprofloxacin, where resistance results from a point mutation in the fluoroquinolone target, DNA gyrase. Cellular reporter assays indicated IMP-1700 inhibited the bacterial SOS-response to DNA damage, and compound-functionalized Sepharose successfully pulled-down the AddAB repair complex. This work provides validation of bacterial DNA repair as a novel therapeutic target and delivers IMP-1700 as a tool molecule and starting point for therapeutic development to address the pressing challenge of antibiotic resistance.
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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.