TXA709
TXA709 is an orally active FtsZ-targeting prodrug that hydrolyzes to the active metabolite TXA707 (HY-153695). TXA709 inhibits bacterial (bacterial) Z-ring cytokinesis by targeting FtsZ, exerts bactericidal activity against Staphylococcus aureus isolates including Vancomycin (HY-B0671)-, Daptomycin (HY-B0108)-, and Linezolid (HY-10394)-resistant strains, and shows synergistic effects when combined with Cefdinir (HY-B0136) or Oxacillin (HY-B0925A). TXA709 can be used for research on MRSA infections and Staphylococcus aureus infections.
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- CAS. Nr.: 1609670-80-5
- Formel: C22H19F5N4O3S
- Molecular Weight:514.47
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Speicherung:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biologische Aktivität
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Biologische Aktivität
Beschreibung
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HeLa | IC50 |
120 μg/mL
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Cytotoxicity against human cervical cancer HeLa cells by four-day continuous MTT assay with IC50 >120 µg/mL.
Cytotoxicity against human cervical cancer HeLa cells by four-day continuous MTT assay with IC50 >120 µg/mL.
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26033735 |
| MDCK | IC50 |
120 μg/mL
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Cytotoxicity against Madin-Darby canine kidney MDCK cells by four-day continuous MTT assay with IC50 >120 µg/mL.
Cytotoxicity against Madin-Darby canine kidney MDCK cells by four-day continuous MTT assay with IC50 >120 µg/mL.
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26033735 |
In Vitro
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
TXA-709 (2.5-160 mg/kg; oral; administered at 6-24 h intervals with observation continued for 24 h) achieved net bacteriostasis against all tested Staphylococcus aureus isolates in a neutropenic mouse thigh infection model, and achieved 1-log10 kill against 4 of 5 isolates, with an AUC/MIC target of 122 for bacteriostasis and an AUC/MIC target of 243 for 1-log10 kill[3].
TXA709 (20 mg/kg; i.v.; administered once 15 minutes post-infection) in combination with 150 mg/kg Oxacillin produced a 100% survival rate[4].
TXA709 (60 mg/kg; i.v.; administered once 1-3 h post-infection) in combination with 600 mg/kg Oxacillin reduced the mouse thigh bacterial burden by approximately 2.3 logs[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:ICR/Swiss (female, 6-week-old, specific pathogen-free, 23-27 g, neutropenic)[3]
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Dosage:10, 40, 160 mg/kg/24 h
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Administration:oral-gastric; 6-, 8-, 12-, or 24-h dosing intervals; 24 h
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Result:Showed AUC/MIC as the PK/PD index most closely linked to efficacy (R2 = 0.72).
Produced very similar dose-response curves for each fractionated dosing regimen.
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Animal Model:ICR/Swiss (female, 6-week-old, specific pathogen-free, 23-27 g, neutropenic)[3]
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Dosage:2.5, 5, 10, 20, 40, 80, 160 mg/kg
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Administration:oral; every 6 h; 24 h
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Result:Produced net stasis against all 5 isolates.
Achieved at least 1-log10 kill in 4 of 5 isolates.
Required static doses of 186-247 mg/kg/24 h.
Required doses of 326-640 mg/kg/24 h for 1-log10 kill.
Showed an AUC/MIC relationship with efficacy across all S. aureus isolates (R2 = 0.74).
Showed mean total 24 h AUC/MIC of 122 for net stasis (free 17.1).
Showed mean total 24 h AUC/MIC of approximately 243 for 1-log10 reduction (free 34).
Did not alter the pharmacodynamic target by beta-lactam resistance.
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Animal Model:Swiss-Webster (female, average weight 25 g)[4]
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Dosage:20 mg/kg (alone); 20 mg/kg plus Oxacillin 60, 90, or 150 mg/kg
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Administration:i.v.; once at 15 min post-infection; oxacillin i.v. at 30 min post-infection
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Result:Resulted in 0% survival (0 out of 5 mice) with TXA709 20 mg/kg alone.
Resulted in 0%, 40%, and 100% survival with TXA709 20 mg/kg plus Oxacillin 60, 90, and 150 mg/kg, respectively.
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Animal Model:Swiss-Webster (female, average weight 25 g, neutropenic)[4]
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Dosage:20 mg/kg (total 60 mg/kg)
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Administration:i.v.; at 1, 2, and 3 h post-infection
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Result:Produced no efficacious response with TXA709 60 mg/kg alone, with thigh bacterial burden similar to vehicle.
Reduced thigh bacterial burden by approximately 2.3 logs relative to vehicle with TXA709 60 mg/kg plus Oxacillin 600 mg/kg.
Chemical Information
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CAS. Nr. 1609670-80-5
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Molecular Weight 514.47
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Formel C22H19F5N4O3S
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SMILES
O=C(C1=C(F)C(OCC2=NC3=C(S2)N=CC(C(F)(F)F)=C3)=CC=C1F)NC(C4CCN(CC4)C)=O
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Please store the product under the recommended conditions in the Certificate of Analysis.
Reinheit & Dokumentation
Verweise
[1]. Kaul M, et al. TXA709, an FtsZ-Targeting Benzamide Prodrug with Improved Pharmacokinetics and Enhanced In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus. Antimicrob Agents Chemother. 2015 Aug;59(8):4845-55. [Content Brief]
[3]. Lepak AJ, et al. In Vivo Pharmacodynamic Evaluation of an FtsZ Inhibitor, TXA-709, and Its Active Metabolite, TXA-707, in a Murine Neutropenic Thigh Infection Model. Antimicrob Agents Chemother. 2015 Oct;59(10):6568-74. [Content Brief]
[4]. Kaul M, et al. Combination with a FtsZ inhibitor potentiates the in vivo efficacy of oxacillin against methicillin-resistant Staphylococcus aureus. Med Chem Res. 2022 Oct;31(10):1705-1715. [Content Brief]
[5]. Bi F, et al. Design, synthesis and structure-based optimization of novel isoxazole-containing benzamide derivatives as FtsZ modulators. European journal of medicinal chemistry. 2018 Nov 05;159:90-103. [Content Brief]
Calculators
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
TXA709 Related Classifications
HY-187955 Related Classifications
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