Eravacycline

For research use only. Not for therapeutic Use.

  • CAT Number: I006700
  • CAS Number: 1207283-85-9
  • Molecular Formula: C27H31FN4O8
  • Molecular Weight: 558.56
  • Purity: ≥95%
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Eravacycline (Cat No.:I006700) is a synthetic tetracycline antibiotic developed for the treatment of bacterial infections. It belongs to the class of antibiotics known as tetracyclines and specifically targets the ribosome, inhibiting protein synthesis in bacteria. Eravacycline has broad-spectrum activity against both Gram-positive and Gram-negative bacteria, including multidrug-resistant strains such as methicillin-resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Enterobacteriaceae (CRE). It has demonstrated efficacy in treating complicated intra-abdominal infections and complicated urinary tract infections in clinical trials. Eravacycline offers a potential therapeutic option for infections caused by resistant bacteria, contributing to the ongoing efforts to combat antibiotic resistance.


Catalog Number I006700
CAS Number 1207283-85-9
Synonyms

TP-434; TP 434; TP434; Eravacycline;(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

Molecular Formula C27H31FN4O8
Purity ≥95%
Target rpsD
Target Protein

P0A7V8

Solubility Soluble in DMSO, not in water
Appearance Solid
Storage Dry, dark and at 2 - 8 °C for six months or -20°C for two years.
Overview of Clinical Research

Originator: Tetraphase Pharmaceuticals<br />
Class: Acetamides; Antibacterials; Pyrrolidines; Small molecules; Tetracyclines<br />
Mechanism of Action: Protein 30S ribosomal subunit inhibitors<br />
Orphan Drug Status: No<br />
New Molecular Entity: Yes<br />
Highest Development Phases: Phase III Urinary tract infections

IC50 MIC50/90: 0.5/1 mg/L
IUPAC Name (4S,4aS,5aR,12aR)-4-(dimethylamino)-7-fluoro-1,10,11,12a-tetrahydroxy-3,12-dioxo-9-[(2-pyrrolidin-1-ylacetyl)amino]-4a,5,5a,6-tetrahydro-4H-tetracene-2-carboxamide
InChI 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/h9,11,13,20,34-35,38,40H,3-8,10H2,1-2H3,(H2,29,39)(H,30,33)/t11-,13-,20-,27-/m0/s1
InChIKey AKLMFDDQCHURPW-ISIOAQNYSA-N
SMILES CN(C)[C@H]1[C@@H]2C[C@@H]3CC4=C(C=C(C(=C4C(=C3C(=O)[C@@]2(C(=C(C1=O)C(=O)N)O)O)O)O)NC(=O)CN5CCCC5)F
Reference

1. Drugs. 2016 Apr;76(5):567-88. doi: 10.1007/s40265-016-0545-8.<br />
Review of Eravacycline, a Novel Fluorocycline Antibacterial Agent.<br />
Zhanel GG(1)(2)(3), Cheung D(4), Adam H(5)(6), Zelenitsky S(4), Golden A(5), Schweizer F(5)(7), Gorityala B(7), Lagac&eacute;-Wiens PR(5)(8), Walkty A(5)(9), Gin AS(5)(4)(10), Hoban DJ(5)(6), Karlowsky JA(5)(8).<br />
Author information:<br />
(1)Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. [email protected]. (2)Department of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada. [email protected]. (3)Department of Clinical Microbiology, Health Sciences Centre, MS673-820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada. [email protected]. (4)Faculty of Science, College of Pharmacy, University of Manitoba, Winnipeg, Manitoba, Canada. (5)Department of Medical Microbiology, College of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada. (6)Department of Clinical Microbiology, Health Sciences Centre, MS673-820 Sherbrook Street, Winnipeg, Manitoba, R3A 1R9, Canada. (7)Department of Chemistry, Faculty of Science, University of Manitoba, Winnipeg, Manitoba, Canada. (8)Department of Clinical Microbiology, Saint Boniface Hospital, Winnipeg, Manitoba, Canada. (9)Department of Medicine, Health Sciences Centre, Winnipeg, Manitoba, Canada. (10)Department of Pharmacy, Health Sciences Centre, Winnipeg, Manitoba, Canada.<br />
Eravacycline is an investigational, synthetic fluorocycline antibacterial agent that is structurally similar to tigecycline with two modifications to the D-ring of its tetracycline core: a fluorine atom replaces the dimethylamine moiety at C-7 and a pyrrolidinoacetamido group replaces the 2-tertiary-butyl glycylamido at C-9. Like other tetracyclines, eravacycline inhibits bacterial protein synthesis through binding to the 30S ribosomal subunit. Eravacycline demonstrates broad-spectrum antimicrobial activity against Gram-positive, Gram-negative, and anaerobic bacteria with the exception of Pseudomonas aeruginosa. Eravacycline is two- to fourfold more potent than tigecycline versus Gram-positive cocci and two- to eightfold more potent than tigecycline versus Gram-negative bacilli. Intravenous eravacycline demonstrates linear pharmacokinetics that have been described by a four-compartment model. Oral bioavailability of eravacycline is estimated at 28 % (range 26-32 %) and a single oral dose of 200 mg achieves a maximum plasma concentration (C max) and area under the plasma concentration-time curve from 0 to infinity (AUC0-&infin;) of 0.23 &plusmn; 0.04 mg/L and 3.34 &plusmn; 1.11 mg&middot;h/L, respectively. A population pharmacokinetic study of intravenous (IV) eravacycline demonstrated a mean steady-state volume of distribution (V ss) of 320 L or 4.2 L/kg, a mean terminal elimination half-life (t &frac12;) of 48 h, and a mean total clearance (CL) of 13.5 L/h. In a neutropenic murine thigh infection model, the pharmacodynamic parameter that demonstrated the best correlation with antibacterial response was the ratio of area under the plasma concentration-time curve over 24 h to the minimum inhibitory concentration (AUC0-24h/MIC). Several animal model studies including mouse systemic infection, thigh infection, lung infection, and pyelonephritis models have been published and demonstrated the in vivo efficacy of eravacycline. A phase II clinical trial evaluating the efficacy and safety of eravacycline in the treatment of community-acquired complicated intra-abdominal infection (cIAI) has been published as well, and phase III clinical trials in cIAI and complicated urinary tract infection (cUTI) have been completed. The eravacycline phase III program, known as IGNITE (Investigating Gram-Negative Infections Treated with Eravacycline), investigated its safety and efficacy in cIAI (IGNITE 1) and cUTI (IGNITE 2). Eravacycline met the primary endpoint in IGNITE 1, while data analysis for IGNITE 2 is currently ongoing. Common adverse events reported in phase I-III studies included gastrointestinal effects such as nausea and vomiting. Eravacycline is a promising intravenous and oral fluorocycline that may offer an alternative treatment option for patients with serious infections, particularly those caused by multidrug-resistant Gram-negative pathogens.<br />
2. Expert Opin Investig Drugs. 2014 Nov;23(11):1575-84. doi: 10.1517/13543784.2014.965253. Epub 2014 Sep 24.<br />
Eravacycline for the treatment of intra-abdominal infections.<br />
Bassetti M(1), Righi E.<br />
Author information:<br />
(1)Santa Maria Misericordia Hospital, Infectious Diseases Division , Piazzale Santa Maria della Misericordia 15, 33100 Udine , Italy +39 0432 559355 ; +39 0432 559360 ; [email protected].<br />
INTRODUCTION: There has been a dramatic increase in the incidence of multidrug-resistant pathogens over the past few years, which highlights the need for new anti-infective therapeutics. Eravacycline is a novel, broad-spectrum synthetic tetracycline indicated for the treatment of severe infections caused by Gram-positive and Gram-negative bacteria.<br />
AREAS COVERED: In this review, the authors report eravacycline/&#39;s pharmacokinetic characteristics and its microbiological spectrum of activity. Furthermore, the authors also highlight the safety and efficacy data from the recent studies on urinary and intra-abdominal infections.<br />
EXPERT OPINION: The profile of eravacycline offers several advantages. Indeed, eravacycline has a broad-spectrum activity toward pathogens involved in complicated urinary tract (cUTIs) and intra-abdominal infections (cIAIs), including extended-spectrum beta-lactamase and carbapenem-resistant Enterobacteriaceae, methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. The availability of an oral formulation supports eravacycline/&#39;s possible use in sequential therapy. High urinary concentrations favor its use in cUTIs and may reduce the overuse of other antimicrobials that may select resistance, such as carbapenems. Eravacycline efficacy and tolerability have been investigated in a Phase II clinical trial in cIAIs comparing two dosages of eravacycline with ertapenem, showing comparable efficacy among the three arms and a low rate of adverse effects. The results of new Phase III studies are awaited to confirm eravacycline/&#39;s future applications in severe nosocomial infections.

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