Gepotidacin is a novel triazaacenaphthylene bacterial type II topoisomerase inhibitor. The compound was developed by GlaxoSmithKline (London, UK) and has broad-spectrum in vitro activity against Gram-positive and Gram-negative bacteria. It has activity against bacteria causing urinary tract infections and gonorrhea. Gepotidacin is a biocompatible polymer that can be used as an antimicrobial agent in wastewater treatment.
Gepotidacin is slightly soluble in DMSO.
| Molecular Formula | C24H28N6O3 |
| Mechanism of Action | Gepotidacin inhibits bacterial DNA replication, targeting DNA gyrase (syn topoisomerase II) GyrA subunit and topoisomerase IV (ParC subunit). These enzymes are integral for bacterial replication, transcription and cell division. |
| Spectrum | Gepotidacin has in vitro activity against Gram-negative and Gram-positive bacteria, including drug-resistant strains. It also has in vitro activity against select Mycoplasmas and Uroplasmas. |
| Microbiology Applications |
Gepotidacin was tested for activity against antibiotic-resistant Neisseria gonorrhoeae, the causal agent of gonorrhea. In vitro activity of Gepotidacin, and its effect of efflux pump inactivation on clinical Neisseria gonorrhoeae isolates compared Gepotidacin with antimicrobials currently or previously recommended for gonorrhoea. Minimum inhibitory concentrations (MICs) (mg/L) were determined via agar dilution and results demonstrated the compound had potent in vitro activity against all gonococcal isolates MIC ≤4 mg/L). The modal MIC, MIC50, MIC90 and MIC range of Gepotidacin were 0.5, 0.5, 1 and 0.032–4 mg/L, respectively. Authors reported no significant cross-resistance between Gepotidacin and any other antimicrobials, including ciprofloxacin (Jacobsson et al, 2018). Gepotidacin has in vitro activity against causative pathogens of acute bacterial skin and skin structure infections (ABSSSIs)(O'Riordan et al, 2017). In vitro activities of Gepotidacin were comparable against methicillin-susceptible and methicillin-resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90 =0.5 μg/ml) (Biedenbach, 2016). Gepotidacin was tested against 85 type strains and clinical isolates of Mycoplasma (M. pneumoniae, M. hominis, M. genitalium) and Ureaplasma (U. parvum, & U. urealyticum in comparison to levofloxacin, moxifloxacin, azithromycin or clindamycin, and tetracycline. Its activity was not affected by resistance to fluoroquinolones, tetracyclines, or macrolides in the strains evaluated (Waites et al, 2017). |
| References |
Biedenbach DJ (2016) In vitro activity of Gepotidacin, a novel triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad-spectrum of bacterial pathogens. Antimicrob Agents Chemother. 2016 60(3):1918-1923 PMID 26729499 Flamm RK et al (2017) Gepotidacin (GSK2140944) In vitro activity against Gram-positive and Gram-negative bacteria. Antimicrob. Agents Chemother. 61(7):e00468-17 PMID: 28483959 Jacobsson S, Golparian D, Scangarella-Oman N, Unemo M (2018) In vitro activity of the novel triazaacenaphthylene Gepotidacin (GSK2140944) against MDR Neisseria gonorrhoeae, J. Antimicrob. Chemother. 73 (8):2072–2077 PMID 29796611 O'Riordan W et al (2017) Efficacy, safety, and tolerability of Gepotidacin (GSK2140944) in the treatment of patients with suspected or confirmed Gram-positive acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 61(6):e02095-16. PMID: 28373199 Waites KB, Crabb DM, Xiao L, Duffy LB (2017) In vitro activities of Gepotidacin (GSK2140944) and other antimicrobial agents against human Mycoplasmas and Ureaplasmas. Antimicrob. Agents Chemother. 61:10.1128/aac.01064-17 |