Zoliflodacin

Overview

Zoliflodacin, sold under the brand name Nuzolvence, is an antibiotic used for the treatment of antibiotic-resistant Neisseria gonorrhoeae (gonorrhea). Zoliflodacin is a spiropyrimidinetrione bacterial type II topoisomerase inhibitor. Zoliflodacin is being developed as part of a public-private partnership between Innoviva Specialty Therapeutics and the Global Antibiotic Research & Development Partnership (GARDP). Zoliflodacin is taken by mouth.[1][2][3] WP

The most common side effects include low white blood cell counts, headache, dizziness, nausea, and diarrhea.[2] WP

Zoliflodacin was approved for medical use in the United States in December 2025. The US Food and Drug Administration considers it to be a first-in-class medication.[2][4][5] WP

Drug class

Antibacterial WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

Zoliflodacin is indicated for the treatment of uncomplicated urogenital gonorrhea due to Neisseria gonorrhoeae in people who weigh at least 35 kg.[1][2] WP⚠ The source also gives this in other units.

Susceptible bacteria

Zoliflodacin has shown in vitro activity against the following species of bacteria: Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, and Chlamydia trachomatis[6] WP

Risks and side effects

Adverse effects

Animal studies showed that zoliflodacin might cause birth defects, pregnancy loss, or male fertility problems.[2] WP

Pharmacology

Mechanism of action

Zoliflodacin is a spiropyrimidinetrione antibacterial agent (first-in-class) that inhibits bacterial type II topoisomerases, including DNA gyrase and topoisomerase IV. It binds to these enzymes at a site that is distinct from fluoroquinolone binding sites, leading to inhibition of DNA replication and bacterial cell death. This novel mechanism confers activity against strains resistant to other topoisomerase inhibitors and involves inhibition of bacterial type II topoisomerases.[6–9] WP

History

History

A high throughput screening campaign aimed at identifying compounds with whole cell antibacterial activity performed at Pharmacia & Upjohn identified compound PNU-286607, a progenitor of Zoliflodacin, as having the desired activity.[10] WP

Subsequent research at AstraZeneca led to the discovery that the nitroaromatic in PNU-286607 could be replaced with a fused benzisoxazole ring, which allowed for an exploration of different groups at the 3-position of the heterocycle. This work was continued at Entasis Pharmaceuticals where extensive optimization resulted in the discovery of ETX0914.[6][11] WP

Researchers tested zoliflodacin in a study with 930 participants who had uncomplicated urogenital gonorrhea. Two-thirds of participants received a single 3-gram dose of zoliflodacin dissolved in water. The other third received the standard treatment of ceftriaxone shot plus azithromycin pill. The study measured how well the medicines cleared the bacteria 4 to 8 days after treatment. The study showed 91% of participants who took zoliflodacin were cured and 96% of participants who received the standard treatment were cured.[2] WP

Legal status

Legal status

Zoliflodacin was approved for medical use in the United States in December 2025.[3][12] WP

The US Food and Drug Administration (FDA) granted the application for zoliflodacin fast track, qualified infectious disease product, and priority review designations for the uncomplicated urogenital gonorrhea indication. The FDA approval for Nuzolvence was granted to Entasis Therapeutics.[2] WP

Names

Zoliflodacin is the international nonproprietary name.[13] WP

Zoliflodacin is sold under the brand name Nuzolvence.[3] WP

Chemistry

Formula

C22H22FN5O7 PC

CAS number

1620458-09-4 PC

Molar mass (g/mol)

487.4 PC

IUPAC name (computed by PubChem)

(4'R,6'S,7'S)-17'-fluoro-4',6'-dimethyl-13'-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]spiro[1,3-diazinane-5,8'-5,15-dioxa-2,14-diazatetracyclo[8.7.0.02,7.012,16]heptadeca-1(17),10,12(16),13-tetraene]-2,4,6-trione PC

SMILES

C[C@@H]1CN2[C@H]([C@@H](O1)C)C3(CC4=CC5=C(C(=C42)F)ON=C5N6[C@H](COC6=O)C)C(=O)NC(=O)NC3=O PC

InChIKey

ZSWMIFNWDQEXDT-ZESJGQACSA-N PC

PubChem CID

76685216

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Nuzolvence- zoliflodacin for suspension. 22 December 2025
2. Journal / agency FDA Approves Two Oral Therapies to Treat Gonorrhea. 12 December 2025
3. Other Pierre G. Nuzolvence (Zoliflodacin) Receives U.S. FDA Approval. 12 December 2025
4. Journal / agency Novel Drug Approvals for 2025. 8 July 2026
5. Journal / agency Advancing Health Through Innovation: New Drug Therapy Approvals 2025. January 2026
6. Journal / agency Basarab GS, Kern GH, McNulty J, Mueller JP, Lawrence K, Vishwanathan K, Alm RA, Barvian K, Doig P, Galullo V, Gardner H, Gowravaram M, Huband M, Kimzey A, Morningstar M, Kutschke A, Lahiri SD, Perros M, Singh R, Schuck VJ, Tommasi R, Walkup G, Newman JV. Responding to the challenge of untreatable gonorrhea: ETX0914, a first-in-class agent with a distinct mechanism-of-action against bacterial Type II topoisomerases. Scientific Reports. July 2015. doi:10.1038/srep11827 · PMID 26168713 · PMC4501059
7. Journal / agency Taylor, R. In Vitro Activity and Mechanism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic. Antimicrobial Agents and Chemotherapy. 2020. doi:10.1128/AAC.00950-20 · PMID 32329999
8. Journal / agency Bradford PA, Miller AA, O'Donnell J, Mueller JP. Zoliflodacin: An Oral Spiropyrimidinetrione Antibiotic for the Treatment of Neisseria gonorrheae, Including Multi-Drug-Resistant Isolates. ACS Infectious Diseases. June 2020. doi:10.1021/acsinfecdis.0c00021 · PMID 32329999
9. Journal / agency Pisano L, Giovannuzzi S, Supuran CT. Management of Neisseria gonorrhoeae infection: from drug resistance to drug repurposing. Expert Opinion on Therapeutic Patents. June 2024. doi:10.1080/13543776.2024.2367005 · PMID 38856987
10. Journal / agency Miller AA, Bundy GL, Mott JE, Skepner JE, Boyle TP, Harris DW, Hromockyj AE, Marotti KR, Zurenko GE, Munzner JB, Sweeney MT, Bammert GF, Hamel JC, Ford CW, Zhong WZ, Graber DR, Martin GE, Han F, Dolak LA, Seest EP, Ruble JC, Kamilar GM, Palmer JR, Banitt LS, Hurd AR, Barbachyn MR. Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors. Antimicrobial Agents and Chemotherapy. August 2008. doi:10.1128/AAC.00247-08 · PMID 18519725 · PMC2493097
11. Journal / agency Basarab GS, Brassil P, Doig P, Galullo V, Haimes HB, Kern G, Kutschke A, McNulty J, Schuck VJ, Stone G, Gowravaram M. Novel DNA gyrase inhibiting spiropyrimidinetriones with a benzisoxazole scaffold: SAR and in vivo characterization. Journal of Medicinal Chemistry. November 2014. doi:10.1021/jm501174m · PMID 25286019
12. Other U.S. FDA Approves Nuzolvence (zoliflodacin), a First-in-Class, Single-dose, Oral Antibiotic for the Treatment of Uncomplicated Urogenital Gonorrhea in Adults and Adolescents. 12 December 2025
13. Journal / agency World Health Organization. International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76. WHO Drug Information. 2016

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.