Zoliflodacin is a novel synthetic antibacterial active pharmaceutical ingredient (API) belonging to the spiropyrimidinetrione class of antibiotics. It is a first-in-class bacterial type II topoisomerase inhibitor developed for the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae. Zoliflodacin was originally developed under the codes AZD0914 and ETX0914 and is now marketed in the United States as NUZOLVENCE.
The U.S. Food and Drug Administration approved Nuzolvence on December 12, 2025, for the treatment of uncomplicated urogenital gonorrhea in adults and pediatric patients 12 years of age and older who weigh at least 35 kg. The approved dosage is a single oral dose of 3 grams.
Zoliflodacin has the molecular formula C22H22FN5O7, CAS Number 1620458-09-4, UNII FWL2263R77, and molecular weight approximately 487.4 g/mol. These identifiers are supported by FDA GSRS, PubChem and the FDA-approved product information.
Zoliflodacin is a structurally complex small molecule containing fluorine, nitrogen and oxygen atoms and a characteristic spiropyrimidinetrione chemical framework. Its chemical name is:
(2R,4S,4aS)-11-Fluoro-1,2,4,4a-tetrahydro-2,4-dimethyl-8-[(4S)-4-methyl-2-oxo-3-oxazolidinyl]spiro[isoxazolo[4,5-g][1,4]oxazino[4,3-a]quinoline-5(6H),5′(2′H)-pyrimidine]-2′,4′,6′(1′H,3′H)-trione.
FDA's CMC review and approved labeling identify this chemical structure, formula and molecular mass.
Zoliflodacin is a stereochemically defined molecule. Its complex tetracyclic/spiro architecture contributes to its distinctive biological activity and physicochemical properties.
Zoliflodacin is classified as a bacterial type II topoisomerase inhibitor and belongs to the spiropyrimidinetrione antibacterial class.
Unlike conventional fluoroquinolone antibiotics, zoliflodacin acts through a distinct interaction with bacterial type II topoisomerases. Its principal antibacterial targets include DNA gyrase and topoisomerase IV, enzymes essential for bacterial DNA replication, chromosome segregation and cell survival.
This novel mechanism is particularly important in the development of alternative treatments for Neisseria gonorrhoeae with resistance to established antibacterial therapies.
Zoliflodacin inhibits bacterial type II topoisomerases, particularly DNA gyrase and topoisomerase IV. These enzymes regulate DNA supercoiling and are essential during bacterial replication and chromosome processing.
By interfering with topoisomerase function, zoliflodacin disrupts bacterial DNA replication and ultimately produces a bactericidal effect.
The compound has a binding mechanism that is distinct from established fluoroquinolone antibiotics. This different target interaction provides zoliflodacin with a novel antibacterial profile and makes it an important development in the search for new treatments against drug-resistant Neisseria gonorrhoeae.
FDA classifies Nuzolvence as a spiropyrimidinetrione bacterial type II topoisomerase inhibitor.
The primary pharmaceutical application of Zoliflodacin is the treatment of uncomplicated urogenital gonorrhea caused by Neisseria gonorrhoeae.
The FDA-approved indication covers adults and pediatric patients 12 years of age and older weighing at least 35 kg. Nuzolvence is administered as a single oral 3 g dose.
The approved product is particularly significant because gonorrhea has developed resistance to multiple antibiotic classes. Zoliflodacin provides an orally administered treatment option with a mechanism distinct from several established antibacterial agents.
Zoliflodacin was initially developed as AZD0914 and later as ETX0914. Development focused on discovering an antibacterial agent with a new mechanism capable of addressing the increasing problem of antimicrobial resistance in Neisseria gonorrhoeae.
The compound progressed through clinical development for uncomplicated gonorrhea and demonstrated activity against susceptible and resistant isolates.
The U.S. FDA subsequently approved Nuzolvence in December 2025, making zoliflodacin one of the important new antibacterial agents introduced for gonorrhea treatment. FDA's 2025 novel drug approval listing identifies Nuzolvence as a novel drug approved for uncomplicated urogenital gonorrhea.
The approved Nuzolvence formulation is supplied as white to off-white granules for oral suspension.
Each unit-dose packet contains 3 g of zoliflodacin. The product must be mixed with water before administration. The approved labeling specifies use of 60 mL of water for preparation of the suspension, followed by administration of the prepared dose.
The finished formulation contains inactive ingredients including colloidal silicon dioxide, croscarmellose sodium, magnesium stearate, mannitol, microcrystalline cellulose, talc and xanthan gum.
These formulation details describe the approved finished drug product and should not be confused with bulk Zoliflodacin API specifications.
Zoliflodacin is a synthetic small-molecule API requiring controlled chemical synthesis, purification and solid-state processing.
Because of its complex molecular structure and multiple stereochemical centers, manufacturing controls should address chemical identity, stereochemical integrity, assay, related substances, residual solvents, water content, elemental impurities and physical characteristics.
The final API should be manufactured under appropriate pharmaceutical quality systems and tested using validated analytical methods suitable for the material and intended regulatory market.
Identity confirmation for Zoliflodacin can use multiple analytical techniques, including:
MedChemExpress provides analytical documentation including RP-HPLC, NP-HPLC, LC-MS, MS, NMR and IR for its research-grade material.
For pharmaceutical manufacturing, identity should be confirmed through validated procedures established in the applicable drug-substance specification.
Zoliflodacin does not currently have a publicly identified USP or Ph. Eur. finished API monograph that establishes a universal numerical assay range. Therefore, numerical specifications should not be presented as pharmacopoeial limits unless supported by an applicable official monograph.
Current commercial analytical sources provide useful reference values. MedChemExpress reports a selected batch with 99.98% purity, 99.98% assay and 99.98% ee, while another commercial raw-material source reports NLT 98.0% HPLC purity. These values represent specific supplier/product specifications and should not be treated as universal regulatory release criteria.
For an SDP API page, the safest professional approach is to distinguish the documented supplier/reference specification from the final manufacturer-approved release specification.
Related-substance control is an important quality attribute for Zoliflodacin API. Process-related impurities can arise from synthetic intermediates, incomplete reactions, degradation products or stereochemical impurities.
A commercial raw-material specification reports:
These values should be identified as a supplier/reference specification rather than a universal pharmacopoeial limit.
For commercial pharmaceutical API production, the actual impurity profile and acceptance criteria should be established through validated analytical methods and the applicable regulatory filing.
A commercial Zoliflodacin raw-material specification reports loss on drying NMT 0.5%. This provides a useful numerical reference for CMS documentation, although it should not be described as an official USP or Ph. Eur. limit without an applicable monograph.
Moisture control can be important for maintaining chemical stability and consistent physical properties of the API. The actual test method and acceptance criterion should follow the approved specification for the manufacturing process.
Zoliflodacin is a stereochemically defined molecule. Stereochemical integrity is therefore an important aspect of API quality.
Current research-grade analytical data report 99.98% enantiomeric excess (ee) for a selected batch. This is a batch-specific analytical result rather than a universal pharmaceutical release specification.
Where stereochemical purity is included in a commercial API specification, a validated chiral analytical method should be used.
The finished Nuzolvence drug product is described by FDA as white to off-white granules.
Bulk API appearance should be defined according to the manufacturer's approved drug-substance specification. Research-grade supplier information describes Zoliflodacin as a solid/powder, with appearance varying from white to off-white or pale material depending on supplier and batch.
For a pharmaceutical API page, the finished-product appearance should not automatically be presented as the bulk API specification.
Zoliflodacin's formulation has been developed as an oral suspension rather than a conventional tablet. The approved product is mixed with water before administration.
The formulation contains multiple excipients that facilitate preparation of a uniform oral suspension. The FDA label specifies preparation using water and administration of the entire prepared dose within the specified time.
API solubility should therefore be described according to the validated drug-substance characterization rather than inferred solely from the finished dosage form.
The FDA CMC review specifies storage of the approved drug product at 20°C to 25°C, with permitted excursions to 15°C to 30°C, under USP controlled-room-temperature conditions. The review supports a 36-month expiration period for the drug product under those conditions.
Bulk Zoliflodacin API should be stored according to its own validated stability data and manufacturer specification. Finished-product storage conditions should not automatically be transferred to bulk API.
Zoliflodacin is an important modern antibacterial API because of its novel mechanism against bacterial type II topoisomerases and its application to uncomplicated gonorrhea.
For pharmaceutical manufacturers, important quality attributes include chemical identity, assay, chromatographic purity, related substances, stereochemical purity, moisture, residual solvents, elemental impurities and solid-state characteristics.
The API should be supported by an appropriate certificate of analysis, validated analytical methods, impurity profile and regulatory documentation.
Zoliflodacin is a specialized antibacterial active pharmaceutical ingredient with increasing pharmaceutical importance following its U.S. approval as Nuzolvence in 2025.
With CAS 1620458-09-4, molecular formula C22H22FN5O7 and molecular weight 487.4 g/mol, Zoliflodacin can be characterized using modern chromatographic, spectroscopic and mass-spectrometric techniques.
For pharmaceutical companies and API procurement teams, Zoliflodacin should be evaluated on the basis of identity, assay, impurity profile, stereochemical purity, moisture, residual solvents, physical characteristics and applicable regulatory requirements.
| Parameter | Specification |
|---|---|
| Appearance | white to off-white crystalline powder |
| Identification | IR & HPLC compliant |
| Assay (HPLC) | NLT 98.0% |
| Loss on Drying | NMT 0.5% |
| Residue on Ignition | NMT 0.1% |
| Individual Impurity | NMT 0.15% |
| Total Impurities | NMT 1.0% |
| Water Content | NMT 0.5% |