ArticleEuropean journal of medicinal chemistry2021
A γ-lactam siderophore antibiotic effective against multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter spp.
Article in European journal of medicinal chemistry, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
What it found
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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
8 citing papers in PubMed, 20 citations in OpenAlex.
- Thiophene-fused γ-lactams inhibit the SARS-CoV-2 main proteaseChemical science · 2024Article
- Drug Discovery in the Field of β-Lactams: An Academic Perspective.Antibiotics (Basel, Switzerland) · 2024Review
- Penicillin-binding protein (PBP) inhibitor development: A 10-year chemical perspective.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- Chelation in Antibacterial Drugs: From Nitroxoline to Cefiderocol and Beyond.Antibiotics (Basel, Switzerland) · 2022Review
- Structural Characterization of the D179N and D179Y Variants of KPC-2 β-Lactamase: Ω-Loop Destabilization as a Mechanism of Resistance to Ceftazidime-Avibactam.Antimicrobial agents and chemotherapy · 2022Article
- The Chemical Relationship Among Beta-Lactam Antibiotics and Potential Impacts on Reactivity and Decomposition.Frontiers in microbiology · 2022Review
- Virulence Potential and Treatment Options of Multidrug-Resistant (MDR)Microorganisms · 2021Review
- Article
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 2 countries.
Funding
Abstract
Serious infections caused by multidrug-resistant (MDR) organisms (Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii) present a critical need for innovative drug development. Herein, we describe the preclinical evaluation of YU253911, 2, a novel γ-lactam siderophore antibiotic with potent antimicrobial activity against MDR Gram-negative pathogens. Penicillin-binding protein (PBP) 3 was shown to be a target of 2 using a binding assay with purified P. aeruginosa PBP3. The specific binding interactions with P. aeruginosa were further characterized with a high-resolution (2.0 Å) X-ray structure of the compound's acylation product in P. aeruginosa PBP3. Compound 2 was shown to have a concentration >1 μg/ml at the 6 h time point when administered intravenously or subcutaneously in mice. Employing a meropenem resistant strain of P. aeruginosa, 2 was shown to have dose-dependent efficacy at 50 and 100 mg/kg q6h dosing in a mouse thigh infection model. Lastly, we showed that a novel γ-lactam and β-lactamase inhibitor (BLI) combination can effectively lower minimum inhibitory concentrations (MICs) against carbapenem resistant Acinetobacter spp. that demonstrated decreased susceptibility to 2 alone.
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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.