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Purity: ≥98%
Gepotidacin (formerly GSK2140944) is a novel, potent, first-in-class, triazaacenaphthylene antibacterial that inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism and has demonstrated in vitro activity against Neisseria gonorrhoeae, including drug-resistant strains, and also targets pathogens associated with other conventional and biothreat infections. Broth microdilution was used to evaluate the MIC and minimum bactericidal concentration (MBC) activity of gepotidacin and comparators against 25 N. gonorrhoeae strains (including five ciprofloxacin-nonsusceptible strains). Gepotidacin activity was also evaluated against three N. gonorrhoeae strains (including a ciprofloxacin-nonsusceptible strain) for resistance development, against three N. gonorrhoeae strains (including two tetracycline- and azithromycin-nonsusceptible strains) using time-kill kinetics and checkerboard methods, and against two N. gonorrhoeae strains for the investigation of postantibiotic (PAE) and subinhibitory (PAE-SME) effects. The MIC50 and MIC90 for gepotidacin against the 25 N. gonorrhoeae isolates tested were 0.12 and 0.25 μg/ml, respectively. The MBC50 and MBC90 for gepotidacin were 0.25 and 0.5 μg/ml, respectively. Gepotidacin was bactericidal, and single-step resistance selection studies did not recover any mutants, indicating a low rate of spontaneous single-step resistance. For combinations of gepotidacin and comparators tested using checkerboard methods, there were no instances where antagonism occurred and only one instance of synergy (with moxifloxacin; fractional inhibitory concentration, 0.375). This was not confirmed by in vitro time-kill studies. The PAE for gepotidacin against the wild-type strain ranged from 0.5 to >2.5 h, and the PAE-SME was >2.5 h. These in vitro data indicate that further study of gepotidacin is warranted for potential use in treating infections caused by N. gonorrhoeae.
| ln Vitro |
Gepotidacin is a novel, first-in-class triazaacenaphthylene antibacterial that targets pathogens linked to other common and biothreat infections. It also inhibits bacterial DNA gyrase and topoisomerase IV through a unique mechanism. It has demonstrated in vitro activity against both gram-positive and gram-negative bacteria, including drug-resistant strains. Against the 25 N. gonorrhoeae isolates tested, the MIC50 and MIC90 values for gepotidacin are 0.12 and 0.25 μg/mL, respectively[1]. The following bacteria have different gepotidacin MIC90s (in μg/mL): Escherichia coli, 2; Moraxella catarrhalis, ≤0.06; Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1[2]. Acute bacterial skin and skin structure infections (ABSSSIs) can be caused by pathogens that gepotidacin is reactive against in vitro[3].
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| ln Vivo |
GSK2140944's minimum inhibitory concentrations (MICs) for the six MRSA isolates range from 0.125 to 0.5 mg/L. The range of ELF penetration ratios is 1.1 to 1.4. In neutropenic mice, maximal decreases of 1.1 to 3.1 log10 CFU have been observed. For stasis and 1-log-unit decreases, the mean fAUC/MIC ratios needed are 59.3 ± 34.6 and 148.4 ± 83.3, respectively.
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| Animal Protocol |
Mice: GSK2140944 s.c. in single doses of 6.25, 50, or 200 mg/kg is given to groups of 48 infected mice at 3 h postinoculation (0 h) for neutropenic pharmacokinetic studies. Using a cardiac puncture, blood samples are taken from groups of six mice at five minutes and 0.25, 0.5, 1, 1.5, 2, 3, and 4 hours after the dose for doses of 6.25 or 50 mg/kg, and at five minutes and 0.25, 0.5, 1, 1.5, 2, 4, and 6 hours after the dose for 200 mg/kg[4].
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| References |
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| Additional Infomation |
Gepotidacin has been used in trials studying the treatment of Gonorrhea, Infections, Bacterial, and Infections, Respiratory Tract.
Drug Indication Treatment of uncomplicated urinary tract infections Treatment of uncomplicated urogenital gonorrhea |
| Molecular Formula |
C24H28N6O3
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|---|---|
| Molecular Weight |
448.5175
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| Exact Mass |
448.222
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| Elemental Analysis |
C, 64.27; H, 6.29; N, 18.74; O, 10.70
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| CAS # |
1075236-89-3
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| Related CAS # |
Gepotidacin (S enantiomer);2319789-82-5
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| PubChem CID |
25101874
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| Appearance |
White to yellow solid powder
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| LogP |
1.415
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
33
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| Complexity |
893
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| Defined Atom Stereocenter Count |
1
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| SMILES |
O=C1C([H])=NC2C([H])=C([H])C(N3C=2N1[C@@]([H])(C3([H])[H])C([H])([H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C1([H])[H])N([H])C([H])([H])C1C([H])=C2C(=C([H])N=1)OC([H])([H])C([H])([H])C2([H])[H])=O
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| InChi Key |
PZFAZQUREQIODZ-LJQANCHMSA-N
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| InChi Code |
InChI=1S/C24H28N6O3/c31-22-4-3-20-24-29(22)15-19(30(24)23(32)13-27-20)14-28-7-5-17(6-8-28)25-11-18-10-16-2-1-9-33-21(16)12-26-18/h3-4,10,12-13,17,19,25H,1-2,5-9,11,14-15H2/t19-/m1/s1
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| Chemical Name |
(2R)-2-[(4-{[(3,4-dihydro-2H-pyrano[2,3-c]pyridin- 6-yl)methyl]amino}piperidin-1-yl)methyl]-1,2-dihydro- 3H,8H-2a,5,8a-triazaacenaphthylene-3,8-dione
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| Synonyms |
GSK-2140944; GSK2140944; GSK 2140944; GSK-2140944E; GSK2140944E; GSK 2140944E; Gepotidacin
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~7.14 mg/mL (~15.92 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 0.71 mg/mL (1.58 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.71 mg/mL (1.58 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. View More
Solubility in Formulation 3: ≥ 0.71 mg/mL (1.58 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 10% DMSO+40% PEG300+5% Tween-80+45% Saline: ≥ 0.71 mg/mL (1.58 mM) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2296 mL | 11.1478 mL | 22.2955 mL | |
| 5 mM | 0.4459 mL | 2.2296 mL | 4.4591 mL | |
| 10 mM | 0.2230 mL | 1.1148 mL | 2.2296 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Time-kill curve for gepotidacin against N. gonorrhoeae (isolate 12584).Antimicrob Agents Chemother.2017 Feb 23;61(3). pii: e02047-16. |
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 Time-kill curve for gepotidacin against isolate N. gonorrhoeae (isolate 12588).Antimicrob Agents Chemother.2017 Feb 23;61(3). pii: e02047-16. |
 Time-kill curve for gepotidacin against isolate N. gonorrhoeae ATCC 49226.Antimicrob Agents Chemother.2017 Feb 23;61(3). pii: e02047-16. |
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