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Purity: =99.37%
| Targets |
Strong antibiotic eryavacycline is effective against isolates of A. baumannii, including those resistant to sulbactam, BAY 41-6551, and SM 7338. Eravacycline is more active than colistin and BAY 41-6551. The MIC50/90 values of eravacycline dihydrochloride are 0.5/1 mg/L [1]. Six E. coli strains with MICs ranging from 0.125 to 0.25 mg/L exhibit inhibitory effects when exposed to eravacycline[2]. Eravacycline dihydrochloride is a synthetic antibiotic that binds to the 30S ribosomal subunit to prevent bacteria from synthesizing proteins. Eravacycline exhibits good activity against significant gram-positive pathogens, such as methicillin-resistant S. aureus, and broad spectrum activity against gram-negative bacteria in the panel, with the exception of P. aeruginosa. Additionally, eravacycline exhibits strong ribosomal inhibition[3].In all species panels, eravacycline exhibits strong broad-spectrum activity against 90% of the isolates (MIC90) at concentrations ranging from ≤0.008 to 2 μg/mL, with the exception of Pseudomonas aeruginosa and Burkholderia cenocepacia, which both have MIC90 values of 32 μg/mL. Eravacycline exhibits efficacy against bacteria that are resistant to multiple drugs, such as those that express extended-spectrum β-lactamases and mechanisms that confer resistance to other antibiotic classes, such as carbapenem resistance[4].
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| ln Vitro |
Strong antibiotic eryavacycline is effective against isolates of A. baumannii, including those resistant to sulbactam, BAY 41-6551, and SM 7338. Eravacycline is more active than colistin and BAY 41-6551. The MIC50/90 values of eravacycline dihydrochloride are 0.5/1 mg/L [1]. Six E. coli strains with MICs ranging from 0.125 to 0.25 mg/L exhibit inhibitory effects when exposed to eravacycline[2]. Eravacycline dihydrochloride is a synthetic antibiotic that binds to the 30S ribosomal subunit to prevent bacteria from synthesizing proteins. Eravacycline exhibits good activity against significant gram-positive pathogens, such as methicillin-resistant S. aureus, and broad spectrum activity against gram-negative bacteria in the panel, with the exception of P. aeruginosa. Additionally, eravacycline exhibits strong ribosomal inhibition[3].In all species panels, eravacycline exhibits strong broad-spectrum activity against 90% of the isolates (MIC90) at concentrations ranging from ≤0.008 to 2 μg/mL, with the exception of Pseudomonas aeruginosa and Burkholderia cenocepacia, which both have MIC90 values of 32 μg/mL. Eravacycline exhibits efficacy against bacteria that are resistant to multiple drugs, such as those that express extended-spectrum β-lactamases and mechanisms that confer resistance to other antibiotic classes, such as carbapenem resistance[4].
The MICs of Eravacycline against six Escherichia coli strains were determined using CLSI microdilution methods. The median MICs ranged from 0.125 to 0.25 µg/mL. [2] |
| ln Vivo |
Several murine infection models demonstrate the efficacy of eravacycline dihydrochloride against Gram-positive and Gram-negative pathogens that are clinically significant. Eravacycline shows 50% protective dose values of ≤1 mg/kg of body weight once a day (q.d.) against Staphylococcus aureus in mouse septicemia models, indicating its effectiveness. In relation to Escherichia coli isolates, the PD50 values range from 1.2 to 4.4 mg/kg q.d[5].
In a neutropenic murine thigh infection model, Eravacycline demonstrated potent efficacy against all six E. coli strains, including multidrug-resistant strains expressing tetracycline-specific efflux, ribosomal protection, and ESBL genotypes. The maximal reduction in bacterial count compared to untreated controls was -4.37 ± 0.48 log₁₀ CFU/thigh, and the maximum kill from time zero was -1.68 ± 0.50 log₁₀ CFU/thigh. Net stasis was achieved against all strains, and a >1-log kill was achieved against five out of six strains. The exposure-response curves were steep, indicating that small increases in drug exposure resulted in large increases in bactericidal activity. [2] |
| Animal Protocol |
Rats: Sprague-Dawley rats are used to determine pharmacokinetic (PK) parameters. After fasting for at least 12 hours, the animals receive a single oral dose of eravacycline (10 mg/kg) or an IV dose (1 mg/kg), and then they participate in a 24-hour sampling scheme. Using the relevant standard curves, TurboIonspray LC/MSMS analysis determines the concentrations of the dosing solution and plasma. Noncompartmental analysis is used to calculate PK parameters[3].
A neutropenic murine thigh infection model was used. Six-week-old, specific-pathogen-free, female ICR/Swiss mice were rendered neutropenic via subcutaneous injections of cyclophosphamide 4 days (150 mg/kg) and 1 day (100 mg/kg) prior to infection. E. coli strains were grown to logarithmic phase, diluted, and 0.1 mL of inoculum (10⁶·² to 10⁶·⁴ CFU/mL) was injected into the thighs of isoflurane-anesthetized mice. Therapy with Eravacycline was initiated 2 hours post-infection. For pharmacokinetic studies, uninfected mice were administered single intraperitoneal (i.p.) doses of Eravacycline (0.2 mL/dose) at 2.5, 5, 10, 20, 40, and 80 mg/kg. Groups of three mice were euthanized at serial time points (1, 2, 3, 4, 6, 8, 12, 18 h) for plasma collection. For dose fractionation studies (to determine PK/PD index), mice infected with E. coli ATCC 25922 received i.p. doses of Eravacycline (total doses ranging from 6.25 to 100 mg/kg/24h) fractionated into regimens of every 6, 8, 12, or 24 hours for 24 hours. For PK/PD magnitude studies, mice infected with one of six E. coli strains received i.p. doses of Eravacycline every 12 hours, with 2-fold increasing doses ranging from 3.125 to 50 mg/kg per administration. In all efficacy studies, mice were euthanized 24 hours after therapy initiation, thighs were aseptically removed, homogenized, and plated for CFU determination. [2] |
| ADME/Pharmacokinetics |
Following a single intraperitoneal injection in mice, eracycline exhibited dose-dependent pharmacokinetic characteristics across a dose range of 2.5 to 80 mg/kg. The maximum plasma concentration (Cmax) ranged from 0.34 mg/L (2.5 mg/kg) to 2.58 mg/L (40 mg/kg). The area under the concentration-time curve (AUC₀–∞) ranged from 2.44 mg·h/L (2.5 mg/kg) to 57.6 mg·h/L (80 mg/kg), showing a linear relationship across the entire dose range (R² = 0.99). The elimination half-life (t₁/₂) ranged from 3.9 hours (2.5 mg/kg) to 17.6 hours (80 mg/kg).
The protein binding rate is concentration-dependent and can be described by the following formula: % free drug = -0.085 ln(total drug concentration) + 0.2752. This formula is used to calculate the free drug concentration in pharmacodynamic analysis. The 24-hour free drug AUC/MIC (fAUC/MIC) was determined to be the PK/PD parameter with the best correlation to efficacy (R² = 0.80). The mean fAUC/MIC values associated with net inhibition and 1-log bactericidal endpoint were 27.97 ± 8.29 and 32.60 ± 10.85, respectively. [2] |
| Toxicity/Toxicokinetics |
In a phase II clinical trial for complicated intra-abdominal infections, intravenous iracycline was shown to be safe and well-tolerated. [5]
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| References |
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| Additional Infomation |
See also: eracycline hydrochloride (note moved to).
Eracycline is a novel synthetic fluorocycline antibiotic with broad-spectrum antibacterial activity, including against strains with tetracycline and other resistance mechanisms (e.g., efflux, ribosome protection). This study used a mouse thigh infection model with neutropenia to identify the pharmacodynamic drivers and therapeutic targets of eracycline against Escherichia coli. The primary pharmacokinetic/pharmacodynamic target identified was the 24-hour free drug AUC/MIC ratio. The steep exposure-response relationship suggests that dosing strategies that achieve target fAUC/MIC values (inhibitory bacterial counts) close to 28 and 33 (1-log bactericidal) may be effective in clinical applications. [2] |
| Molecular Formula |
C27H33CL2FN4O8
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|---|---|
| Molecular Weight |
631.48
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| Exact Mass |
630.165
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| Elemental Analysis |
C, 51.36; H, 5.27; Cl, 11.23; F, 3.01; N, 8.87; O, 20.27
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| CAS # |
1334714-66-7
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| Related CAS # |
Eravacycline;1207283-85-9
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| PubChem CID |
56951485
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| Appearance |
Light yellow to yellow solid powder
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| Hydrogen Bond Donor Count |
8
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
42
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| Complexity |
1200
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| Defined Atom Stereocenter Count |
4
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| SMILES |
Cl.Cl.FC1=CC(=C(C2=C1C[C@@H]1C(=C2O)C([C@@]2(C(=C(C(N)=O)C([C@H]([C@@H]2C1)N(C)C)=O)O)O)=O)O)NC(CN1CCCC1)=O
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| InChi Key |
JYCNMRVZELJVAW-RZVFYPHASA-N
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| InChi Code |
InChI=1S/C27H31FN4O8.2ClH/c1-31(2)20-13-8-11-7-12-14(28)9-15(30-16(33)10-32-5-3-4-6-32)21(34)18(12)22(35)17(11)24(37)27(13,40)25(38)19(23(20)36)26(29)39;;/h9,11,13,20,34,36-37,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33);2*1H/t11-,13-,20-,27-;;/m0../s1
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| Chemical Name |
(4S,4aS,5aR,12aS)-4-(Dimethylamino)-7-fluoro-3,10,12,12a-tetrahydroxy-1,11-dioxo-9-((pyrrolidin-1-ylacetyl)amino)-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide dihydrochloride
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| Synonyms |
TP-434-046; TP 434-046; TP434-046; TP-434; TP 434; TP434; Eravacycline HCl; Eravacycline hydrochloride.
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. (3). This product is not stable in solution, please use freshly prepared working solution for optimal results. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~158.36 mM)
DMSO : ≥ 50 mg/mL (~79.18 mM） |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5.5 mg/mL (8.71 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 5.5 mg/mL (8.71 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 55.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 5.5 mg/mL (8.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 5.5 mg/mL (8.71 mM) Solubility in Formulation 5: 50 mg/mL (79.18 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5836 mL | 7.9179 mL | 15.8358 mL | |
| 5 mM | 0.3167 mL | 1.5836 mL | 3.1672 mL | |
| 10 mM | 0.1584 mL | 0.7918 mL | 1.5836 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Single-dose plasma pharmacokinetics of eravacycline.
In vivodose fractionation with eravacycline using a neutropenic murine thigh infection model.Antimicrob Agents Chemother.2017 Jun 27;61(7). pii: e00250-17. |
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 Impact of pharmacodynamic regression of thein vivodose fractionation study with eravacycline against E. coli ATCC 25922.Antimicrob Agents Chemother.2017 Jun 27;61(7). pii: e00250-17. |
 In vivodose-effect of eravacycline against six E. coli (EC) strains using a neutropenic murine thigh infection model.
In vivodose-effect of eravacycline against six E. coli isolates using a neutropenic murine thigh infection model.Antimicrob Agents Chemother.2017 Jun 27;61(7). pii: e00250-17. |
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