Zoliflodacin

Structural formula
General
Non-proprietary name	Zoliflodazine
other names	AZD0914; ETX0914;
Molecular formula	C 22 H 22 FN 5 O 7
External identifiers / databases
PubChem	76685216
DrugBank	DB12817
Wikidata	Q27278240
Drug information
Drug class	antibiotic
properties
Molar mass	487.44 g mol −1
safety instructions
GHS hazard labeling ; no classification available
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Zoliflodacin (development codes AZD0914 and ETX0914) is a newly developed, not yet approved antibiotic by AstraZeneca . Chemically it is a spiro-pyrimidine trione. The drug can be administered orally. The biological availability is 97.8%. Some of it is metabolized by the liver and 79.6% is excreted in the stool . 18.2% are eliminated via the kidneys .

Zoliflodacin has a novel mechanism of action. It inhibits bacterial topoisomerase type 2, an enzyme that is indispensable for DNA duplication during reproduction.

In a study, patients with urogenital gonorrhea (infection with Neisseria gonorrhoeae ) were compared with ceftriaxone , a proven antibiotic. Treatment of gonorrhea is becoming increasingly problematic with the development of resistance to antibiotics. Therefore, the FDA (American Medicines Agency) has initiated accelerated approval of zoliflodacin. Zoliflodacin was found to be as effective as ceftriaxone in genitourinary and rectal infections. Zoliflodacin was less effective for pharyngeal infections.

Individual evidence

↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ Gregory S. Basarab, Patrick Brassil, Peter Doig, Vincent Galullo, Howard B. Haimes: Novel DNA Gyrase Inhibiting Spiropyrimidinetriones with a Benzisoxazole Scaffold: SAR and in Vivo Characterization . October 17, 2014, doi : 10.1021 / jm501174m (English).
↑ AstraZeneca: AZ0914 investigator's brochure . Ed .: AstraZeneca. Edition No. 2. Cambridge, England 2014.
↑ Douglas J. Biedenbach, Michael D. Huband, Meredith Hackel, Boudewijn LM de Jonge, Daniel F. Sahm: In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase / Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram- Negative pathogen . In: Antimicrobial Agents and Chemotherapy . tape 59 , no. 10 , October 2015, p. 6053-6063 , doi : 10.1128 / AAC.01016-15 , PMID 26195518 , PMC 4576048 (free full text).
↑ Gregory S. Basarab, Gunther H. Kern, John McNulty, John P. Mueller, Kenneth Lawrence, Karthick Vishwanathan, Richard A. Alm, Kevin Barvian, Peter Doig, Vincent Galullo, Humphrey Gardner, Madhusudhan Gowravaram, Michael Huband, Amy Kimzey , Marshall Morningstar, Amy Kutschke, Sushmita D. Lahiri, Manos Perros, Renu Singh, Virna JA Schuck, Ruben Tommasi, Grant Walkup, Joseph V. Newman: Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases . In: Scientific Reports . 5, 2015, p. 11827. doi : 10.1038 / srep11827 . PMID 26168713 . PMC 4501059 (free full text).
↑ Stephanie N. Taylor, Jeanne Marrazzo, Byron E. Batteiger, Edward W. Hook, Arlene C. Seña, Jill Long, Michael R. Wierzbicki, Hannah Kwak, Shacondra M. Johnson, Kenneth Lawrence, John Mueller: Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea . In: New England Journal of Medicine . 379, No. 19, 2018, pp. 1835–1845. doi : 10.1056 / NEJMoa1706988 . PMID 30403954 .

[NV-1] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[2] Gregory S. Basarab, Patrick Brassil, Peter Doig, Vincent Galullo, Howard B. Haimes: Novel DNA Gyrase Inhibiting Spiropyrimidinetriones with a Benzisoxazole Scaffold: SAR and in Vivo Characterization . October 17, 2014, doi : 10.1021 / jm501174m (English).

[3] AstraZeneca: AZ0914 investigator's brochure . Ed .: AstraZeneca. Edition No. 2. Cambridge, England 2014.

[4] Douglas J. Biedenbach, Michael D. Huband, Meredith Hackel, Boudewijn LM de Jonge, Daniel F. Sahm: In Vitro Activity of AZD0914, a Novel Bacterial DNA Gyrase / Topoisomerase IV Inhibitor, against Clinically Relevant Gram-Positive and Fastidious Gram- Negative pathogen . In: Antimicrobial Agents and Chemotherapy . tape 59 , no. 10 , October 2015, p. 6053-6063 , doi : 10.1128 / AAC.01016-15 , PMID 26195518 , PMC 4576048 (free full text).

[5] Gregory S. Basarab, Gunther H. Kern, John McNulty, John P. Mueller, Kenneth Lawrence, Karthick Vishwanathan, Richard A. Alm, Kevin Barvian, Peter Doig, Vincent Galullo, Humphrey Gardner, Madhusudhan Gowravaram, Michael Huband, Amy Kimzey , Marshall Morningstar, Amy Kutschke, Sushmita D. Lahiri, Manos Perros, Renu Singh, Virna JA Schuck, Ruben Tommasi, Grant Walkup, Joseph V. Newman: Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases . In: Scientific Reports . 5, 2015, p. 11827. doi : 10.1038 / srep11827 . PMID 26168713 . PMC 4501059 (free full text).

[6] Stephanie N. Taylor, Jeanne Marrazzo, Byron E. Batteiger, Edward W. Hook, Arlene C. Seña, Jill Long, Michael R. Wierzbicki, Hannah Kwak, Shacondra M. Johnson, Kenneth Lawrence, John Mueller: Single-Dose Zoliflodacin (ETX0914) for Treatment of Urogenital Gonorrhea . In: New England Journal of Medicine . 379, No. 19, 2018, pp. 1835–1845. doi : 10.1056 / NEJMoa1706988 . PMID 30403954 .