| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
Eravacycline (formerly known as TP-434; TP434; trade name: Xerava) is a novel fluorocycline with a broad-spectrum of antimicrobial activity against panels of recently isolated aerobic and anaerobic Gram-negative and Gram-positive bacteria. It was approved by FDA in August 2018 to treat complicated intra-abdominal infections in patients 18 years of age and older. Eravacycline showed 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). The antibacterial activity of eravacycline was minimally affected by expression of tetracycline-specific efflux and ribosomal protection mechanisms in clinical isolates. Furthermore, eravacycline was active against multidrug-resistant bacteria, including those expressing extended-spectrum β-lactamases and mechanisms conferring resistance to other classes of antibiotics, including carbapenem resistance. Eravacycline has the potential to be a promising new intravenous (i.v.)/oral antibiotic for the empirical treatment of complicated hospital/health care infections and moderate-to-severe community-acquired infections.
| Targets |
Tetracycline; Bacterial 30S ribosomal subunit, inhibiting bacterial protein synthesis . Unlike other tetracyclines, eravacycline effectively evades common tetracycline-specific resistance mechanisms, including efflux pumps and ribosomal protection
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|---|---|
| ln Vitro |
Strong antibiotic eravacycline works against isolates of A. baumannii, including those resistant to levofloxacin, imipenem/meropenem, sulbactam, and amikacin/tobramycin. Eravacycline exhibits higher activity than colistin, levofloxacin, amikacin, tobramycin, and comparators in the tetracycline class. The MIC50/90 values of eravacycline 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 Vivo |
Every 12 hours, mice are given eravacycline at two-fold increasing doses (ranging from 3.125 to 50 mg/kg). The 1-log kill endpoint and net stasis are associated with mean fAUC/MIC magnitudes of 32.60±10.85 and 27.97±8.29, respectively[2]. Eravacycline effectively combats both Gram-positive and Gram-negative pathogens that are clinically significant in a variety of murine infection models. In mouse models of septicemia, eravacycline is effective; it shows 50% protective dose values of ≤1 mg/kg of body weight once daily (q.d.) against Streptococcus pyogenes and Tetracycline-resistant isolates of methicillin-resistant S. aureus (MRSA). In relation to Escherichia coli isolates, the PD50 values range from 1.2 to 4.4 mg/kg q.d[5].
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| Cell Assay |
Broth Microdilution Method: The CLSI broth microdilution method is used to determine the minimum inhibitory concentrations (MICs) of eravacycline against various bacterial clinical isolates. Bacteria are inoculated in culture media containing eravacycline (concentration range 0.001-32 μg/mL) and incubated at 35°C for 18-24 hours before MIC reading .
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| Animal Protocol |
Rats [3]
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. |
| ADME/Pharmacokinetics |
Pharmacokinetic parameters of eravacycline in healthy volunteers and patients are as follows :
Peak concentration (Cmax): 1.29 ± 0.40 μg/mL (after 1.0 mg/kg every 12 hours for 7 doses) ; also reported as 1,100 ± 13.5 ng/mL
Area under the curve (AUC): 4.56 ± 0.94 μg·h/mL (at steady state) ; AUC₀–∞ of 4,380 ± 11.4 h·ng/mL
Elimination half-life (t₁/₂): 18.2 ± 5.0 hours
Clearance (CL): 228 ± 13.8 mL/min (total clearance) ; renal clearance is approximately 41.9 ± 16.6 mL/min
Volume of distribution at steady state (Vss): 217 ± 4.9 L
Metabolites: Primary metabolites include TP-498 (Cmax 20.4 ng/mL) and TP-6208 (AUC 1,780 h·ng/mL)
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| Toxicity/Toxicokinetics |
Common Adverse Reactions: The most common adverse events are gastrointestinal intolerance (primarily nausea, vomiting, and diarrhea), occurring in 51.3% of patients in clinical studies .
Warnings and Precautions:
Hypersensitivity reactions: May include rash, urticaria, difficulty breathing, swelling of the face/lips/tongue/throat
Hepatotoxicity: Manifested as dark urine, fatigue, loss of appetite, stomach pain, jaundice
Increased intracranial pressure: May present with headache, blurred vision, double vision, or vision loss
Tooth discoloration: Contraindicated in children under 8 years of age; may cause permanent yellow-gray-brown tooth discoloration
Pregnancy and lactation: Contraindicated during pregnancy; breastfeeding should be avoided for at least 4 days after the last dose
Other Adverse Effects: Less common but serious side effects include Clostridioides difficile-associated diarrhea (antibiotic-associated), pancreatitis symptoms (severe abdominal/back pain, nausea, vomiting), and renal function changes (altered urine output) .
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| References |
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| Additional Infomation |
Eravacycline belongs to the tetracycline class of antibiotics. Eravacycline is a tetracycline antibacterial drug. See also: Eravacycline (note moved to); Eravacycline dihydrochloride (note moved to).
Drug Indications Eravacycline is indicated for the treatment of complicated intra-abdominal infections (cIAI) in adults. Official guidelines for the rational use of antibacterial drugs should be followed. |
| Molecular Formula |
C27H31FN4O8
|
|---|---|
| Molecular Weight |
558.56
|
| Exact Mass |
558.212
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| Elemental Analysis |
C, 58.06; H, 5.59; F, 3.40; N, 10.03; O, 22.91
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| CAS # |
1207283-85-9
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| Related CAS # |
Eravacycline dihydrochloride;1334714-66-7
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| PubChem CID |
54726192
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| Appearance |
Solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
868.1±65.0 °C at 760 mmHg
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| Flash Point |
478.8±34.3 °C
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| Vapour Pressure |
0.0±0.3 mmHg at 25°C
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| Index of Refraction |
1.711
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| LogP |
0.25
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| Hydrogen Bond Donor Count |
6
|
| Hydrogen Bond Acceptor Count |
11
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
40
|
| Complexity |
1200
|
| Defined Atom Stereocenter Count |
4
|
| SMILES |
FC1C([H])=C(C(=C2C=1C([H])([H])[C@@]1([H])C(=C2O[H])C([C@@]2(C(=C(C(N([H])[H])=O)C([C@]([H])([C@@]2([H])C1([H])[H])N(C([H])([H])[H])C([H])([H])[H])=O)O[H])O[H])=O)O[H])N([H])C(C([H])([H])N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H])=O
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| InChi Key |
HLFSMUUOKPBTSM-ISIOAQNYSA-N
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| InChi Code |
InChI=1S/C27H31FN4O8/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)/t11-,13-,20-,27-/m0/s1
|
| 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
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| Synonyms |
TP-434-046; TP 434-046; TP434-046; TP-434; TP 434; TP434; Eravacycline free base
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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 |
| 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) |
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.7903 mL | 8.9516 mL | 17.9032 mL | |
| 5 mM | 0.3581 mL | 1.7903 mL | 3.5806 mL | |
| 10 mM | 0.1790 mL | 0.8952 mL | 1.7903 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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