gepotidacin  (MedChemExpress)

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Structures of the fluoroquinolone ciprofloxacin, NBTI OSUAB-0284, and triazaacenaphthylene gepotidacin.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques:

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on DNA cleavage mediated by wild-type B. anthracis gyrase. Levels of single-stranded (filled circles, SSB) and double-stranded DNA breaks (open circles, DSB) induced by OSUAB-0284 (left panel), gepotidacin (middle panel), and ciprofloxacin (right panel) are shown. Error bars represent the standard deviation of at least 3 independent experiments. A representative gel of gyrase-mediated DNA cleavage with each compound is shown above the corresponding graph. DNA represents the negatively supercoiled DNA control. The positions of nicked (Nick), linear (Lin), and negatively supercoiled [(−)­SC] plasmid are indicated. Levels of DNA cleavage were adjusted for baseline cleavage in the absence of drugs.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Standard Deviation, Control, Plasmid Preparation

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on DNA supercoiling catalyzed by wild-type B. anthracis gyrase. The inhibition of catalytic activity by OSUAB-0284 (left panel), gepotidacin (middle panel), and ciprofloxacin (right panel) is shown. Error bars represent the standard deviation of at least 3 independent experiments. IC 50 values (drug concentration at which enzyme activity is inhibited by 50%), including the standard error of the mean, for each assay are shown in the respective panels. A representative gel of gyrase-catalyzed DNA supercoiling with each compound is shown above the corresponding graph. DNA represents the fully relaxed DNA control. The positions of relaxed (Relax) and negatively supercoiled [(−)­SC] plasmids are indicated.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Inhibition, Activity Assay, Standard Deviation, Concentration Assay, Control

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on DNA cleavage mediated by wild-type B. anthracis topoisomerase IV. Levels of single-stranded (filled circles, SSB) and double-stranded DNA breaks (open circles, DSB) induced by OSUAB-0284 (left panel), gepotidacin (middle panel), and ciprofloxacin (right panel) are shown. Error bars represent the standard deviation of at least 3 independent experiments. A representative gel of topoisomerase IV-mediated DNA cleavage with each compound is shown above the corresponding graph. DNA represents the negatively supercoiled DNA control. The positions of nicked (Nick), linear (Lin), and negatively supercoiled [(−)­SC] plasmid are indicated. Levels of DNA cleavage were adjusted for baseline cleavage in the absence of drugs.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Standard Deviation, Control, Plasmid Preparation

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on DNA decatenation catalyzed by wild-type B. anthracis topoisomerase IV. The inhibition of catalytic activity by OSUAB-0284 (left panel), gepotidacin (middle panel), and ciprofloxacin (right panel) is shown. Error bars represent the standard deviation of at least 3 independent experiments. IC 50 values (drug concentration at which enzyme activity is inhibited by 50%), including the standard error of the mean, for each assay are shown in the respective panels. A representative gel of topoisomerase IV-catalyzed decatenation with each compound is shown above the corresponding graph. DNA represents the fully catenated (Cat) DNA control. The position of decatenated (Decat) DNA is indicated.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Inhibition, Activity Assay, Standard Deviation, Concentration Assay, Control

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on the activities of WT and fluoroquinolone-resistant mutants of B. anthracis gyrase. (A) Levels of single-stranded DNA breaks induced by OSUAB-0284 (left panel) and gepotidacin (right panel) are shown for WT gyrase (black) and fluoroquinolone-resistant mutant enzymes that harbor GyrA S85L (blue) or GyrA E89K (red). A summary table displays the EC 50 and adjusted maximal DNA cleavage values. (B) The inhibition of supercoiling by OSUAB-0284 (left panel) and gepotidacin (right panel) are shown for wild-type gyrase (black) and fluoroquinolone-resistant mutant enzymes that harbor GyrA S85L (blue) or GyrA E89K (red). Error bars represent the standard deviation of at least 3 independent experiments. A summary table displays IC 50 values (drug concentration at which enzyme activity is inhibited by 50%), including the standard error of the mean, for each assay.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Mutagenesis, Inhibition, Standard Deviation, Concentration Assay, Activity Assay

Journal: ACS Infectious Diseases

Article Title: Activities of the Novel Bacterial Topoisomerase Inhibitor OSUAB-0284 against the Biothreat Pathogen Bacillus anthracis and Its Type II Topoisomerases

doi: 10.1021/acsinfecdis.5c00860

Figure Lengend Snippet: Effects of OSUAB-0284, gepotidacin, and ciprofloxacin on the activities of WT and fluoroquinolone-resistant mutants of B. anthracis topoisomerase IV. (A) Levels of single-stranded DNA breaks induced by OSUAB-0284 (left panel) and gepotidacin (right panel) are shown for WT gyrase (black) and fluoroquinolone-resistant mutant enzymes that harbor GyrA S81Y (purple) or GyrA E85K (green). Error bars represent the standard deviation of at least 3 independent experiments. A summary table displays the EC 50 and adjusted maximal DNA cleavage values. (B) The inhibition of decatenation by OSUAB-0284 (left panel) and gepotidacin (right panel) are shown for WT topoisomerase IV (black) and fluoroquinolone-resistant mutant enzymes that harbor GyrA S81Y (purple) and GyrA E85K (green). Error bars represent the standard deviation of at least 3 independent experiments. A summary table displays IC 50 values (drug concentration at which enzyme activity is inhibited by 50%), including the standard error of the mean, for each assay.

Article Snippet: Gepotidacin (MedChemExpress) was stored at −20 °C as a 6 mM stock solution in 100% DMSO.

Techniques: Mutagenesis, Standard Deviation, Inhibition, Concentration Assay, Activity Assay

Journal: Drugs

Article Title: Antibacterials with Novel Chemical Scaffolds in Clinical Development

doi: 10.1007/s40265-024-02137-x

Figure Lengend Snippet: Overlay of the crystal structures of moxifloxacin (green), zoliflodacin (yellow) and gepotidacin (pink) in a ternary complex with S. aureus DNA gyrase (GyrA: beige; GyrB: coral) and doubly nicked DNA (blue) with magnesium (purple) (PDB: 5CDQ, 8BP2, and 6QTK) [ – ]

Article Snippet: Gepotidacin is a triazaacenaphthylene (Fig. ) developed by GlaxoSmithKline [ ].

Techniques:

Journal: Drugs

Article Title: Antibacterials with Novel Chemical Scaffolds in Clinical Development

doi: 10.1007/s40265-024-02137-x

Figure Lengend Snippet: Structure of gepotidacin

Article Snippet: Gepotidacin is a triazaacenaphthylene (Fig. ) developed by GlaxoSmithKline [ ].

Techniques:

Journal: International Journal of Molecular Sciences

Article Title: How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites

doi: 10.3390/ijms252111688

Figure Lengend Snippet: Twenty published P6 1 S. aureus DNA gyrase GyrB27–A56(GKdel) structures. Four re-refined structures (*-v2-BA-x.pdb*) are highlighted (underlined structures are available with standard BA-x nomenclature from ‘Research’ tab at https://profiles.cardiff.ac.uk/staff/baxb —click to download (accessed on 10 October 2024).

Article Snippet: In GlaxoSmithKline, the development of the NBTI gepotidacin was problematic because of the general hERG (and other ion channel) inhibition of the class [ ].

Techniques: Sequencing

Journal: International Journal of Molecular Sciences

Article Title: How Do Gepotidacin and Zoliflodacin Stabilize DNA Cleavage Complexes with Bacterial Type IIA Topoisomerases? 1. Experimental Definition of Metal Binding Sites

doi: 10.3390/ijms252111688

Figure Lengend Snippet: A model of gepotidacin binding to DNA before forming the complex with S. aureus DNA-gyrase. ( a ) Gepotidacin and GSK299423 structures compared. LHS—left-hand side; RHS—right-hand side. ( b ) A model of gepotidacin (yellow carbons) bound to DNA. The basic nitrogen has been modelled interacting (dotted red line) with a phosphate of the DNA backbone. ( c ) Gepotidacin bound to S. aureus DNA gyrase and DNA; the basic nitrogen interacts with one of the Asp 83 s (dotted red line).

Article Snippet: In GlaxoSmithKline, the development of the NBTI gepotidacin was problematic because of the general hERG (and other ion channel) inhibition of the class [ ].

Techniques: Binding Assay