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Ozenoxacin (formerly known as GF-001001-00; M-5120; T-3912; trade names Ozanex; Ozewid; Xepi) is a novel nonfluorinated topical quinolone class of antibiotic. In December 2017, Ozenoxacin wa approved by FDA to treat impetigo. Ozenoxacin is active against some bacteria that have developed resistance to currently used quinolone and fluoroquinolone antibiotics. Compared with the activities of other quinolones against well-characterized quinolone-susceptible and quinolone-resistant Gram-positive bacteria, ozenoxacin was 3-fold to 321-fold more active than other quinolones. Ozenoxacin could represent a first-in-class nonfluorinated quinolone for the topical treatment of a broad range of dermatological infections.
Physicochemical Properties
| Molecular Formula | C21H21N3O3 |
| Molecular Weight | 363.42 |
| Exact Mass | 363.158 |
| Elemental Analysis | C, 69.41; H, 5.82; N, 11.56; O, 13.21 |
| CAS # | 245765-41-7 |
| Related CAS # | Ozenoxacin-d3 |
| PubChem CID | 9863827 |
| Appearance | Solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 573.5±50.0 °C at 760 mmHg |
| Flash Point | 300.7±30.1 °C |
| Vapour Pressure | 0.0±1.7 mmHg at 25°C |
| Index of Refraction | 1.694 |
| LogP | 3.41 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 6 |
| Rotatable Bond Count | 4 |
| Heavy Atom Count | 27 |
| Complexity | 645 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | O=C(C1=CN(C2CC2)C3=C(C=CC(C4=CC(C)=C(NC)N=C4)=C3C)C1=O)O |
| InChi Key | XPIJWUTXQAGSLK-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C21H21N3O3/c1-11-8-13(9-23-20(11)22-3)15-6-7-16-18(12(15)2)24(14-4-5-14)10-17(19(16)25)21(26)27/h6-10,14H,4-5H2,1-3H3,(H,22,23)(H,26,27) |
| Chemical Name | 1-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid |
| Synonyms | GF-001001-00; M 5120; GF-001001-00; M-5120; M-5120; GF001001-00; M5120; GF-001001 00; T-3912; GF-00100100; Ozenoxacin; trade name: Xepi |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Quinolone |
| ln Vitro | With MICs ranging from 0.008 to 4 mg/L, ozenoxacin (OZN) exhibits strong antibacterial activity against clinical isolates of Gram-positive microorganisms. When it comes to MRSA, MSSA, MSSE, and MRSE strains that have two, three, or four mutations in the gyrA and grlA (parC) genes, ozenoxacin exhibits good activity[1]. MSSA and S. agalactiae strains are inhibited by ozenoxacin, with resistance rates of >10−10 and 5.3 × 10−10, respectively. Zeenoxacin's maximum MIC value for mutant strains is 8 mg/L[2]. |
| ADME/Pharmacokinetics |
Absorption, Distribution and Excretion Four studies were performed in which varying strengths of ozenoxacin cream, up to 2% (twice the concentration of the marketed formulation), were administered to 110 patients. Three of the studies examined systemic absorption in healthy subjects and in subjects having impetigo. The studies were performed with either single or repeated application of up to 1 g ozenoxacin cream to intact or abraded skin (up to 200 cm squared surface area). No systemic absorption was seen in 84 of 86 subjects, and negligible systemic absorption was seen at the level of detection (0.489 ng/mL) in 2 subjects. Studies regarding elimination and excretion have not yet been investigated in humans due to the negligible systemic absorption observed in clinical studies. Ozenoxacin undergoes negligible systemic absorption after its topical administration. Subsequently, since negligible systemic absorption of ozenoxacin was observed in clinical studies, tissue distribution has not been investigated in humans either. Ozenoxacin undergoes negligible systemic absorption after its topical administration. Metabolism / Metabolites Studies have demonstrated that ozenoxacin is not metabolized in the presence of fresh human skin discs and is minimally metabolized in human hepatocytes. |
| Toxicity/Toxicokinetics |
Effects During Pregnancy and Lactation ◉ Summary of Use during Lactation No information is available on ozenoxacin cream during breastfeeding. Because ozenoxacin is poorly absorbed after topical application, it is not likely to reach the bloodstream of the infant or cause any adverse effects in breastfed infants after maternal application away from the breast. Although quinolones are generally acceptable for systemic use, ozenoxacin should be avoided on the nipple because the infant could ingest the drug via licking. ◉ Effects in Breastfed Infants Relevant published information was not found as of the revision date. ◉ Effects on Lactation and Breastmilk Relevant published information was not found as of the revision date. Protein Binding The plasma protein binding of [14 C]-ozenoxacin is moderate at ~80-85% and does not appear to be dependent on concentration. |
| References |
[1]. In vitro activity of Ozenoxacin against quinolone-susceptible and quinolone-resistant gram-positive bacteria. Antimicrob Agents Chemother. 2013 Dec;57(12):6389-92. [2]. In vitro selection of mutants resistant to ozenoxacin compared with levofloxacin and ciprofloxacin in Gram-positive cocci. J Antimicrob Chemother. 2015 Jan;70(1):57-61. |
| Additional Infomation |
Ozenoxacin is a member of quinolines. To date, ozenoxacin has been used in trials studying the treatment of impetigo. As of December 11, 2017 the FDA approved Ferrer Internacional S.A.'s Xepi (ozenoxacin 1%) as a topically applied cream indicated for the treatment of impetigo caused by *Staphylococccus aureus* or *Streptococcus pyogenes* in adult and pediatric patients 2 months of age and older. Despite being a common and highly contagious bacerial skin infection that affects millions of children and adults in the United States each year, ozenoxacin cream is a novel, non-fluorinated quinolone that has demonstrated safe and effective therapy in both the adult and pediatric population. Ozenoxacin is a Quinolone Antimicrobial. Drug Indication Ozenoxacin cream is indicated for the topical treatment of impetigo caused by *Staphylococcus aureus* or *Streptococcus pyogenes* in patients aged 2 months of age and older. FDA Label Treatment of impetigo Mechanism of Action Ozenoxacin is a quinolone antibiotic drug. And, like most quinolones, ozenoxacin predominately executes its mechanism of action by entering into bacterial cells and acting to inhibit the bacterial DNA replication enzymes DNA gyrase A and topoisomerase IV. As DNA gyrase A and topoisomerase IV are essential to bacterial DNA replication activities including supercoiling, supercoil relaxation, chromosomal condensation, chromosomal decatenation and more, their inhibition is the principal action of ozenoxacin's mechanism and it has been demonstrated to be bactericidal against *S. aureus* and *S. pyogenes* organisms. Pharmacodynamics Although the exposure response relationship for ozenoxacin after it has been applied topically has not yet been studied, a formal relationship is unlikely because systemic exposure of ozenoxacin following its topical application has been measured to be negligible. |
Solubility Data
| Solubility (In Vitro) | DMSO : 2.86 ~5 mg/mL (7.87~ 13.75 mM ) |
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7516 mL | 13.7582 mL | 27.5164 mL | |
| 5 mM | 0.5503 mL | 2.7516 mL | 5.5033 mL | |
| 10 mM | 0.2752 mL | 1.3758 mL | 2.7516 mL |