Eravacycline Dihydrochloride is the dihydrochloride salt of Eravacycline, a third-generation tetracycline antibiotic with broad-spectrum activity. It is a derivative of tetracycline that has additional fluorine atoms, a fluorocycline (syn: 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline). It was developed by Tetraphase Pharmaceuticals and was approved by the FDA in 2018.
Eravacycline DiHCl is soluble in water.
| Mechanism of Action |
Tetracycline antibiotics inhibit bacterial growth by disrupting codon-anticodon interactions at the ribosome, thus blocking protein synthesis. Specifically, they bind to a single site on the 30S ribosomal subunit and inhibit protein synthesis by blocking the attachment of charged aminoacyl-tRNA to the A site on the ribosome. Thus, they prevent introduction of new amino acids to the nascent peptide chain. The compound has antibacterial properties against multidrug resistant (MDR) Gram-positive and Gram-negative isolates. Eravacycline was designed to overcome resistance to common tetracycline-specific efflux and ribosomal protection mechanisms via its unique chemical modifications at C-9 and C-7 of the tetracycline core. It maintains high binding affinity to the bacterial ribosome even in presence of ribosomal protection proteins (RPPs). |
| Spectrum |
Broad-spectrum activity against both Gram-positive and Gram-negative bacteria, both aerobic and anaerobic pathogens including the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA). It is active against multidrug-resistant bacteria including those expressing extended-spectrum beta-lactamases. |
| Microbiology Applications |
Eravacycline had potent broad-spectrum activity against 90% of the isolates (MIC90) in panels of all major bacterial species (aerobic, anaerobic, Gram-negative, Gram-positive for a total of 2644 isolates including clinical isolates) and MIC90s were <= 2 ug/ml with the exception of Pseudomonas aeruginosa and Burkholderia cenocepacia (Sutcliffe et al, 2013). MIC values were determined by microtiter microdilution broth (aerobic) or agar dilution (anaerobic) methods. Structurally similar to tigecycline but with multiple times the efficacy against Gram-positive cocci and Gram-negative bacilli, Eravacycline acts as a protein synthesis inhibitor causing bacteriostatic effects at lower concentrations and bactericidal effects only at high concentrations (Zhanel et al, 2016). |
| Molecular Formula | C27H31FN4O8 X 2HCl |
| References |
Jabarin A et al (2024) Eravacycline, an antibacterial drug, repurposed for pancreatic cancer therapy: Insights from a molecular-based deep learning model. Briefings in Bioinformatics 25(3): bbae108 Seifert H, Stefanik D, Sutcliffe JA, Higgins PG (2018) In-vitro activity of the novel fluorocycline Eravacycline against carbapenem non-susceptible Acinetobacter baumannii. Int. J. Antimicrob. Agents. 51(1):62-64 PMID 28705668 Sutcliffe JA, O'Brien W, Fyfe C, Grossman TH (2013) Antibacterial activity of Eravacycline (TP-434), a novel fluorocycline, against hospital and community pathogens. Antimicrob. Agents Chemother. 57(11):5548-5558 PMID 23979750 Xiao XY et al (2012) Fluorocyclines. 1. 7-fluoro-9-pyrrolidinoacetamido-6-demethyl-6-deoxytetracycline: a potent, broad spectrum antibacterial agent. J Med. Chem. 55(2):597-605 PMID 22148514 Varghese D, Sunny D, Kurian A, Cherian T, Varghese L (2023) An in silico study on reproposing eravacycline as an MMP inhibitor. J. Appl. Pharm. Sci. 13(01):232–240 Zhanel GG, Cheung D, Adam H et al (2016) Review of Eravacycline, a novel fluorocycline antibacterial agent. Drugs 76:567–588 |
