gepotidacin   Click here for help

GtoPdb Ligand ID: 10817

Synonyms: Blujepa® | GSK-2140944 | GSK2140944
Approved drug PDB Ligand
gepotidacin is an approved drug
Compound class: Synthetic organic
Comment: Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that inhibits bacterial DNA gyrase and topoisomerase IV via a unique mechanism [2-3]. It was developed for potential to treat conventional and biothreat pathogens including MRSA, respiratory tract infections, acute bacterial skin and skin structure infections (ABSSI) [6,8], and uncomplicated urogenital gonorrhea [5].

gepotidacin is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 4
Hydrogen bond donors 1
Rotatable bonds 5
Topological polar surface area 94.28
Molecular weight 448.22
XLogP 1.63
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=c1cnc2c3n1[C@H](CN1CCC(CC1)NCc1ncc4c(c1)CCCO4)Cn3c(=O)cc2
Isomeric SMILES O=c1cnc2c3n1[C@H](CN1CCC(CC1)NCc1ncc4c(c1)CCCO4)Cn3c(=O)cc2
InChI 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
InChI Key PZFAZQUREQIODZ-LJQANCHMSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Biedenbach DJ, Bouchillon SK, Hackel M, Miller LA, Scangarella-Oman NE, Jakielaszek C, Sahm DF. (2016)
In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens.
Antimicrob Agents Chemother, 60 (3): 1918-23. [PMID:26729499]
2. Farrell DJ, Sader HS, Rhomberg PR, Scangarella-Oman NE, Flamm RK. (2017)
In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae.
Antimicrob Agents Chemother, 61 (3). [PMID:28069643]
3. Gibson EG, Bax B, Chan PF, Osheroff N. (2019)
Mechanistic and Structural Basis for the Actions of the Antibacterial Gepotidacin against Staphylococcus aureus Gyrase.
ACS Infect Dis, 5 (4): 570-581. [PMID:30757898]
4. Hackel MA, Karlowsky JA, Canino MA, Sahm DF, Scangarella-Oman NE. (2022)
In Vitro Activity of Gepotidacin against Gram-Negative and Gram-Positive Anaerobes.
Antimicrob Agents Chemother, 66 (2): e0216521. [PMID:34930028]
5. 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]
6. O'Riordan W, Tiffany C, Scangarella-Oman N, Perry C, Hossain M, Ashton T, Dumont E. (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). [PMID:28373199]
7. Scangarella-Oman NE, Hossain M, Hoover JL, Perry CR, Tiffany C, Barth A, Dumont EF. (2022)
Dose Selection for Phase III Clinical Evaluation of Gepotidacin (GSK2140944) in the Treatment of Uncomplicated Urinary Tract Infections.
Antimicrob Agents Chemother, 66 (3): e0149221. [PMID:34978887]
8. Scangarella-Oman NE, Ingraham KA, Tiffany CA, Tomsho L, Van Horn SF, Mayhew DN, Perry CR, Ashton TC, Dumont EF, Huang J et al.. (2020)
In Vitro Activity and Microbiological Efficacy of Gepotidacin from a Phase 2, Randomized, Multicenter, Dose-Ranging Study in Patients with Acute Bacterial Skin and Skin Structure Infections.
Antimicrob Agents Chemother, 64 (3). [PMID:31818823]