ArticleAntimicrobial agents and chemotherapy2015
In Vivo Pharmacodynamic Evaluation of an FtsZ Inhibitor, TXA-709, and Its Active Metabolite, TXA-707, in a Murine Neutropenic Thigh Infection Model.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Pharmacophore-based virtual screening, molecular docking, MD simulation, MM-GBSA energy calculation and DFT analysis for theRSC advances · 2026Article
- Antibacterial drug discovery: challenges and preclinical promises from synthetic small molecules.Chemical Society reviews · 2026Review
- Identification of a New FtsZ Inhibitor by Virtual Screening, Mechanistic Insights, and Structure-Activity Relationship Analyses.ACS infectious diseases · 2025Article
- Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research.Angewandte Chemie (International ed. in English) · 2025Review
- A Review of Antibacterial Candidates with New Modes of Action.ACS infectious diseases · 2024Review
- Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action.eLife · 2024Article
- Computational docking of FtsZ: Survey of promising antibiotic compounds.Biochemistry and biophysics reports · 2024Article
- Treatment of MRSA Infection: Where are We?Current medicinal chemistry · 2024Review
- Antibiotics in the clinical pipeline as of December 2022.The Journal of antibiotics · 2023Review
- Models versus pathogens: how conserved is the FtsZ in bacteria?Bioscience reports · 2023Review
- Evaluation of 2,6-difluoro-3-(oxazol-2-ylmethoxy)benzamide chemotypes as Gram-negative FtsZ inhibitors.The Journal of antibiotics · 2022Article
- β-Lactams against the Fortress of the Gram-PositiveChemical reviews · 2021Review
- Antibiotics in the clinical pipeline in October 2019.The Journal of antibiotics · 2020Review
- Efficient Synthesis of Amine-Linked 2,4,6-Trisubstituted Pyrimidines as a New Class of Bacterial FtsZ Inhibitors.ACS omega · 2017Article
- The structural assembly switch of cell division protein FtsZ probed with fluorescent allosteric inhibitors.Chemical science · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibiotics with novel mechanisms of action are urgently needed. Processes of cellular division are attractive targets for new drug development. FtsZ, an integral protein involved in cell cytokinesis, is a representative example. In the present study, the pharmacodynamic (PD) activity of an FtsZ inhibitor, TXA-709, and its active metabolite, TXA-707, was evaluated in the neutropenic murine thigh infection model against 5 Staphylococcus aureus isolates, including both methicillin-susceptible and methicillin-resistant isolates. The pharmacokinetics (PK) of the TXA-707 active metabolite were examined after oral administration of the TXA-709 prodrug at 10, 40, and 160 mg/kg of body weight. The half-life ranged from 3.2 to 4.4 h, and the area under the concentration-time curve (AUC) and maximum concentration of drug in serum (Cmax) were relatively linear over the doses studied. All organisms exhibited an MIC of 1 mg/liter. Dose fractionation demonstrated the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) to be the PD index most closely linked to efficacy (R(2) = 0.72). Dose-dependent activity was demonstrated against all 5 isolates, and the methicillin-resistance phenotype did not alter the pharmacokinetic/pharmacodynamic (PK/PD) targets. Net stasis was achieved against all isolates and a 1-log10 kill level against 4 isolates. PD targets included total drug 24-h AUC/MIC values of 122 for net stasis and 243 for 1-log10 killing. TXA-709 and TXA-707 are a promising novel antibacterial class and compound for S. aureus infections. These results should prove useful for design of clinical dosing regimen trials.
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