Quinolone
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].

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].

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Ozenoxacin demonstrated potent in vitro activity against a collection of 50 quinolone-susceptible (QS) and quinolone-resistant (QR) Gram-positive clinical isolates. The minimum inhibitory concentration (MIC) values ranged from 0.008 to 4 mg/L. [1]
Against methicillin-susceptible Staphylococcus aureus (MSSA) QS strains, the MIC of ozenoxacin was 0.008 mg/L. Against MSSA QR strains (with a Ser84Leu mutation in GyrA and high-level resistance to other quinolones), the MICs of ozenoxacin ranged from 0.12 to 2 mg/L. [1]
Against methicillin-resistant S. aureus (MRSA) QR strains (with a Ser84Leu mutation in GyrA), the MICs of ozenoxacin were between 0.06 and 0.12 mg/L. For one MRSA strain with four mutations (GyrA: Ser84Leu, Glu88Lys; ParC: Ser80Phe, Glu84Val), the MIC was 2 mg/L. [1]
Against Streptococcus pyogenes, MICs ranged from 0.03 mg/L (QS strains) to 0.25 mg/L (QR strain with Ser81Phe in GyrA and Ser79Phe in ParC). [1]
Against Streptococcus agalactiae, MICs ranged from 0.03 mg/L (QS strains) to 1 mg/L (QR strains with Ser81Leu in GyrA and Ser79Phe in ParC). [1]
Against Enterococcus faecium, MICs ranged from 0.06 mg/L (QS strain) to 4 mg/L (QR strains with Ser83Ile in GyrA and Ser80Ile in ParC). [1]
The activity of ozenoxacin was 3-fold to 321-fold higher than that of moxifloxacin, levofloxacin, and ciprofloxacin against the tested strains. Its activity was maintained against strains with up to 4 mutations in the GyrA and ParC genes. [1]
The MIC of ozenoxacin was not affected by the presence of the efflux pump inhibitor reserpine (25 mg/L) in most strains, indicating it is not a substrate for common reserpine-inhibited efflux pumps in these bacteria. [1]

The primary cell-based assay was the broth microdilution method for determining Minimum Inhibitory Concentrations (MICs). Bacterial strains were grown aerobically at 37°C in brain heart infusion (BHI) broth. Susceptibility testing for ozenoxacin and comparator quinolones (moxifloxacin, levofloxacin, ciprofloxacin) was performed according to CLSI standards. The MIC was defined as the lowest concentration of antibiotic that inhibited visible growth after incubation. [1]
To assess the impact of efflux pumps, the MICs were also determined in the presence and absence of 25 mg/L of the efflux pump inhibitor reserpine. [1]
Additionally, to characterize resistance mechanisms, the quinolone resistance-determining regions (QRDRs) of the gyrA, gyrB, parC, and parE genes were amplified by polymerase chain reaction (PCR) using previously described primers. The amplified products were then sequenced to identify amino acid substitutions associated with quinolone resistance. [1]

Absorption, Distribution and Excretion
Four studies were conducted on 110 patients using oxaliplatin cream at varying concentrations, up to 2% (twice the concentration of commercially available formulations). Three of these studies examined systemic absorption in healthy subjects and patients with impetigo. In these studies, subjects applied up to 1 gram of oxaliplatin cream to intact or broken skin (up to 200 square centimeters) in single or multiple applications. No systemic absorption was observed in 84 of the 86 subjects, and the systemic absorption in two subjects was extremely low, reaching the detection limit (0.489 ng/mL). Due to the extremely low systemic absorption observed in clinical studies, elimination and excretion studies have not been conducted in humans. Systemic absorption of oxaliplatin after topical application is extremely low. Subsequently, due to the negligible systemic absorption of oxaliplatin observed in clinical studies, tissue distribution in humans was not studied. Systemic absorption of oxaliplatin after topical administration is negligible.

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Metabolism/Metabolites
Studies have shown that oxaliplatin is not metabolized in the presence of fresh human skin discs, and is also metabolized very little in human liver cells.

Effects During Pregnancy and Lactation
◉ Overview of use during lactation There is currently no information regarding the use of oxaliplatin cream during lactation. Because oxaliplatin is poorly absorbed after topical application, it is unlikely to enter the infant's bloodstream, nor will it have any adverse effects on the breastfeeding infant if the mother applies the medication to areas away from the breast. While quinolones can generally be used systemically, oxaliplatin should be avoided on the nipples, as the infant may ingest the drug through licking. ◉ Effects on breastfed infants As of the revision date, no relevant published information was found. ◉ Effects on lactation and breast milk As of the revision date, no relevant published information was found. Protein binding [14C]-oxaliplatin has moderate plasma protein binding, approximately 80-85%, and appears to be concentration-independent.

[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.

Ozenoxacin belongs to the quinolone class of drugs. To date, Ozenoxacin has been used in clinical trials for the treatment of impetigo. As of December 11, 2017, the U.S. Food and Drug Administration (FDA) approved Ferrer Internacional SA's Xepi (1% Ozenoxacin) cream for the treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes, in adults and children aged 2 months and older. Although impetigo is a common and highly contagious bacterial skin infection affecting millions of children and adults in the United States each year, Ozenoxacin cream is a novel non-fluoroquinolone drug that has been proven safe and effective in treating both adults and children. Ozenoxacin is a quinolone antibacterial drug.

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Drug Indications
Ozenoxacin cream is indicated for the topical treatment of impetigo caused by Staphylococcus aureus or Streptococcus pyogenes in patients aged 2 months and older.

FDA Label
Treatment of Impetigo
Mechanism of Action
Ofloxacin is a quinolone antibiotic. Like most quinolones, oxaliplatin's primary mechanism of action is through entry into bacterial cells and inhibition of bacterial DNA replicases DNA gyrase A and topoisomerase IV. Since DNA gyrase A and topoisomerase IV are essential for bacterial DNA replication activities (including supercoiling, supercoiling relaxation, chromosome condensation, chromosome unwinding, etc.), inhibition of these is oxaliplatin's primary mechanism of action, and it has been shown to have bactericidal activity against Staphylococcus aureus and Streptococcus pyogenes.
Pharmacodynamics
Although the exposure-response relationship following topical application of oxaliplatin has not been studied, a formal relationship is unlikely due to the negligible systemic exposure following topical application.

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Oxaliplatin (1-Cyclopropyl-8-methyl-7-[5-methyl-6-(methylamino)-3-pyridyl]-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid) is a novel non-fluorinated topical quinolone antibacterial agent with a pyridyl group at the C-7 position. [1]
This drug was initially developed for the topical treatment of skin infections and, as of the time of this writing, has successfully completed Phase III clinical trials in adults and children with impetigo. [1]
The study concluded that oxaliplatin exhibited excellent in vitro activity against major pathogens causing skin and soft tissue infections (SSTIs), including methicillin-resistant and quinolone-resistant strains. [1]

C21H21N3O3

363.42

363.158

C, 69.41; H, 5.82; N, 11.56; O, 13.21

245765-41-7

Ozenoxacin-d3

9863827

Solid powder

1.4±0.1 g/cm3

573.5±50.0 °C at 760 mmHg

300.7±30.1 °C

0.0±1.7 mmHg at 25°C

1.694

3.41

2

6

4

27

645

0

O=C(C1=CN(C2CC2)C3=C(C=CC(C4=CC(C)=C(NC)N=C4)=C3C)C1=O)O

XPIJWUTXQAGSLK-UHFFFAOYSA-N

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)

1-cyclopropyl-8-methyl-7-(5-methyl-6-(methylamino)pyridin-3-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid

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

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : 2.86 ~5 mg/mL (7.87~ 13.75 mM )

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)