Zoliflodacin

Last updated

Zoliflodacin
Zoliflodacin.svg
Clinical data
Trade names Nuzolvence
Other namesAZD0914; ETX0914
AHFS/Drugs.com nuzolvence
License data
Routes of
administration 		By mouth
Drug class Antibacterial
ATC code
  • None
Legal status
Legal status
Pharmacokinetic data
Bioavailability 97.8%
Metabolism Liver
Onset of action
  • Fasted: 1.5–2.3 h
  • Fed: 4 h
Elimination half-life 5.3–6.3 h
Excretion
Identifiers
  • (2'R,4'S,4'aS)-11'-fluoro-2',4'-dimethyl-8'-[(4S)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-1',2',4',4'a-tetrahydro-6'H-spiro[1,3-diazinane-5,5'-[1,4]oxazino[4,3-a][1,2]oxazolo[4,5-g]quinoline]-2,4,6-trione
CAS Number
PubChem CID
DrugBank
UNII
KEGG
ChEMBL
Chemical and physical data
Formula C22H22FN5O7
Molar mass 487.444 g·mol−1
3D model (JSmol)
  • C[C@@H]1CN2[C@H]([C@@H](O1)C)C3(CC4=C2C(=C5C(=C4)C(=NO5)N6[C@H](COC6=O)C)F)C(=O)NC(=O)NC3=O
  • InChI=1S/C22H22FN5O7/c1-8-7-33-21(32)28(8)17-12-4-11-5-22(18(29)24-20(31)25-19(22)30)16-10(3)34-9(2)6-27(16)14(11)13(23)15(12)35-26-17/h4,8-10,16H,5-7H2,1-3H3,(H2,24,25,29,30,31)/t8-,9+,10-,16+/m0/s1
  • Key:ZSWMIFNWDQEXDT-ZESJGQACSA-N

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

Contents

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

Zoliflodacin was approved for medical use in the United States in December 2025. [2]

Medical uses

Zoliflodacin is indicated for the treatment of uncomplicated urogenital gonorrhea in people who weigh at least 77 pounds (35 kg). [2]

Susceptible bacteria

Zoliflodacin has shown in vitro activity against the following species of bacteria: [4] Staphylococcus aureus , Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , Neisseria gonorrhoeae , and Chlamydia trachomatis

Adverse effects

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

Mechanism of action

Zoliflodacin is a spiropyrimidinetrione antibacterial agent (first-in-class) that inhibits bacterial type II topoisomerases, including DNA gyrase and topoisomerase IV. [5] 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. [6] This novel mechanism confers activity against strains resistant to other topoisomerase inhibitors and involves inhibition of bacterial type II topoisomerases. [4] [7]

History

Compound PNU-286607, discovered in a high-throughput screen for compounds with antibiotic activity. ChiralPNU.png
Compound PNU-286607, discovered in a high-throughput screen for compounds with antibiotic activity.

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. [8]

Subsequent research at AstraZeneca led to the discovery that the nitroaromatic in PNU-286607 could be replaced with a fused benzisoxazole ring, [9] 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. [4]

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

Society and culture

Zoliflodacin was approved for medical use in the United States in December 2025. [3] [10]

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. [2] The FDA approval for zoliflodacin was granted to Entasis Therapeutics. [2]

Names

Zoliflodacin is the international nonproprietary name. [11]

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

References

  1. ↑ "Highlights of prescribing information - NUZOLVENCE (zoliflodacin) for oral suspension" (PDF). innovivaspecialtytherapeutics.com.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "FDA Approves Two Oral Therapies to Treat Gonorrhea". U.S. Food and Drug Administration (FDA) (Press release). 12 December 2025. Retrieved 13 December 2025.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  3. 1 2 3 Pierre G (12 December 2025). "Nuzolvence (Zoliflodacin) Receives U.S. FDA Approval". Global Antibiotic Research & Development Partnership (GARDP). Retrieved 13 December 2025.
  4. 1 2 3 Basarab GS, Kern GH, McNulty J, Mueller JP, Lawrence K, Vishwanathan K, et al. (July 2015). "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. 5 (1) 11827. Bibcode:2015NatSR...511827B. doi:10.1038/srep11827. PMC   4501059 . PMID   26168713.
  5. ↑ Taylor R (2020). "In Vitro Activity and Mechanism of Zoliflodacin, a Novel Spiropyrimidinetrione Antibiotic". Antimicrobial Agents and Chemotherapy. 64 (10). doi:10.1128/AAC.00950-20. PMID   32329999.
  6. ↑ Bradford PA, Miller AA, O'Donnell J, Mueller JP (June 2020). "Zoliflodacin: An Oral Spiropyrimidinetrione Antibiotic for the Treatment of Neisseria gonorrheae, Including Multi-Drug-Resistant Isolates". ACS Infectious Diseases. 6 (6): 1332–1345. doi: 10.1021/acsinfecdis.0c00021 . PMID   32329999.
  7. ↑ Pisano L, Giovannuzzi S, Supuran CT (June 2024). "Management of Neisseria gonorrhoeae infection: from drug resistance to drug repurposing". Expert Opinion on Therapeutic Patents. 34 (6): 511–524. doi:10.1080/13543776.2024.2367005. PMID   38856987.
  8. ↑ Miller AA, Bundy GL, Mott JE, Skepner JE, Boyle TP, Harris DW, et al. (August 2008). "Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors". Antimicrobial Agents and Chemotherapy. 52 (8): 2806–2812. doi:10.1128/AAC.00247-08. PMC   2493097 . PMID   18519725.
  9. ↑ Basarab GS, Brassil P, Doig P, Galullo V, Haimes HB, Kern G, et al. (November 2014). "Novel DNA gyrase inhibiting spiropyrimidinetriones with a benzisoxazole scaffold: SAR and in vivo characterization". Journal of Medicinal Chemistry. 57 (21): 9078–9095. doi:10.1021/jm501174m. PMID   25286019.
  10. ↑ "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" (Press release). Innoviva Specialty Therapeutics. 12 December 2025. Retrieved 28 December 2025– via Business Wire.
  11. ↑ World Health Organization (2016). "International nonproprietary names for pharmaceutical substances (INN): recommended INN: list 76". WHO Drug Information. 30 (3). hdl: 10665/331020 .

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