ETX2514 is a broad-spectrum β-lactamase inhibitor for the treatment of drug-resistant Gram-negative bacteria including Acinetobacter baumannii.

Autor:	Durand-Réville TF; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Guler S; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Comita-Prevoir J; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Chen B; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Bifulco N; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Huynh H; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Lahiri S; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Shapiro AB; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., McLeod SM; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Carter NM; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Moussa SH; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Velez-Vega C; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Olivier NB; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., McLaughlin R; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Gao N; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Thresher J; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Palmer T; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Andrews B; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Giacobbe RA; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Newman JV; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Ehmann DE; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., de Jonge B; AstraZeneca, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., O'Donnell J; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Mueller JP; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Tommasi RA; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA., Miller AA; Entasis Therapeutics, 35 Gatehouse Drive, Waltham, Massachusetts 02451, USA.
Jazyk:	angličtina
Zdroj:	Nature microbiology [Nat Microbiol] 2017 Jun 30; Vol. 2, pp. 17104. Date of Electronic Publication: 2017 Jun 30.
DOI:	10.1038/nmicrobiol.2017.104
Abstrakt:	Multidrug-resistant (MDR) bacterial infections are a serious threat to public health. Among the most alarming resistance trends is the rapid rise in the number and diversity of β-lactamases, enzymes that inactivate β-lactams, a class of antibiotics that has been a therapeutic mainstay for decades. Although several new β-lactamase inhibitors have been approved or are in clinical trials, their spectra of activity do not address MDR pathogens such as Acinetobacter baumannii. This report describes the rational design and characterization of expanded-spectrum serine β-lactamase inhibitors that potently inhibit clinically relevant class A, C and D β-lactamases and penicillin-binding proteins, resulting in intrinsic antibacterial activity against Enterobacteriaceae and restoration of β-lactam activity in a broad range of MDR Gram-negative pathogens. One of the most promising combinations is sulbactam-ETX2514, whose potent antibacterial activity, in vivo efficacy against MDR A. baumannii infections and promising preclinical safety demonstrate its potential to address this significant unmet medical need.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu