Eravacycline  (Synonyms: TP-434)

Eravacycline is a potent and broad-spectrum antibacterial agent.

Eravacycline is potent antibiotic against A. baumannii, including isolates that are resistant to sulbactam, imipenem/meropenem, levofloxacin, and amikacin/tobramycin. Eravacycline shows greater activity than the comparators of the tetracycline class, levofloxacin, amikacin, tobramycin, and colistin. The eravacycline MIC₅₀/₉₀ values are 0.5/1 mg/L^[1]. Eravacycline shows inhibitory effects on six E. coli with MICs ranging from 0.125 to 0.25 mg/L^[2]. Eravacycline dihydrochloride is a synthetic antibiotic, with inhibits bacterial protein synthesis through binding to the 30S ribosomal subunit. Eravacycline displays broad spectrum activity against gram-negative bacteria in the panel except P. aeruginosa, as well as excellent activity against major gram-positive pathogens, including methicillin-resistant S. aureus. Eravacycline also displays potent ribosomal inhibition^[3]. Eravacycline shows potent broad-spectrum activity against 90% of the isolates (MIC₉₀) in each panel at concentrations ranging from ≤0.008 to 2 μg/mL for all species panels except those of Pseudomonas aeruginosa and Burkholderia cenocepacia (MIC₉₀ values of 32 μg/mL for both organisms). Eravacycline is active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Mice are treated with two-fold increasing doses (range 3.125 to 50 mg/kg) of eravacycline every 12 hours. The mean fAUC/MIC magnitude associated with net stasis and 1-log kill endpoint are 27.97±8.29 and 32.60±10.85, respectively^[2]. Eravacycline is active in multiple murine models of infection against clinically important Gram-positive and Gram-negative pathogens. Eravacycline is efficacious in mouse septicemia models, demonstrating 50% protective dose values of ≤1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus, including tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA), and Streptococcus pyogenes. The PD₅₀ values against Escherichia coli isolates are 1.2 to 4.4 mg/kg q.d^[5].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

558.56

C₂₇H₃₁FN₄O₈

1207283-85-9

Solid

Light yellow to yellow

O=C(NC(C(O)=C1C2=O)=CC(F)=C1C[C@@]3([H])C[C@@]4([H])[C@H](N(C)C)C(O)=C(C(N)=O)C([C@@]4(O)C(O)=C32)=O)CN5CCCC5

Room temperature in continental US; may vary elsewhere.

-20°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

• [1]. Seifert H, et al. In-vitro activity of the novel fluorocycline eravacycline against carbapenem non-susceptible Acinetobacter baumannii. Int J Antimicrob Agents. 2017 Jul 10.  [Content Brief]

  [2]. Zhao M, et al. In Vivo Pharmacodynamic Target Assessment of Eravacycline against Escherichia coli in a Murine Thigh Infection Model. Antimicrob Agents Chemother. 2017 Jun 27;61(7).  [Content Brief]

  [3]. Xiao XY, et al. Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent. J Med Chem. 2012 Jan 26;55(2):597-605.  [Content Brief]

  [4]. Sutcliffe JA, et al. Antibacterial activity of eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob Agents Chemother. 2013 Nov;57(11):5548-58.  [Content Brief]

  [5]. Grossman TH, et al. Eravacycline (TP-434) is efficacious in animal models of infection. Antimicrob Agents Chemother. 2015 May;59(5):2567-71.  [Content Brief]