Details
Stereochemistry | ABSOLUTE |
Molecular Formula | C24H28N6O3 |
Molecular Weight | 448.5175 |
Optical Activity | UNSPECIFIED |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Charge | 0 |
SHOW SMILES / InChI
SMILES
O=C1C=CC2=C3N1C[C@@H](CN4CCC(CC4)NCC5=CC6=C(OCCC6)C=N5)N3C(=O)C=N2
InChI
InChIKey=PZFAZQUREQIODZ-LJQANCHMSA-N
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
Molecular Formula | C24H28N6O3 |
Molecular Weight | 448.5175 |
Charge | 0 |
Count |
|
Stereochemistry | ABSOLUTE |
Additional Stereochemistry | No |
Defined Stereocenters | 1 / 1 |
E/Z Centers | 0 |
Optical Activity | UNSPECIFIED |
Gepotidacin (formerly GSK2140944) is a novel, first-in-class, triazaacenaphthylene antibacterial that selectively inhibits bacterial DNA gyrase and topoisomerase IV by a unique mechanism, one that is not utilized by any currently approved human therapeutic agent. As a consequence of its novel mode of action, gepotidacin is active in vitro against target pathogens carrying resistance determinants to established antibacterials, including fluoroquinolones. Gepotidacin has demonstrated in vitro activity against key pathogens, including drug-resistant strains, associated with a range of conventional and biothreat infections. GlaxoSmithKline is developing Gepotidacin for the treatment of gonorrhoea and skin and soft tissue infections.
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2311224 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28069643 |
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Target ID: CHEMBL2363076 Sources: https://www.ncbi.nlm.nih.gov/pubmed/28069643 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Curative | Unknown Approved UseUnknown |
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Curative | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
3.2 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
3.91 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
5.54 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
7.084 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.7 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
2.58 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
3.26 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
2.76 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.65 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
4.498 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
5.306 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
1.29 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
AUC
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.9 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
19.5 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
25.4 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
28.55 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
14.1 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
14.33 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
16.33 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.78 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.82 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
14.84 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
22.37 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8.04 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
T1/2
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
9.07 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8.52 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
8.21 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
11.06 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
7.18 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: MALE food status: FED |
|
9.71 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
8.73 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
6.75 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
|
11.5 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
10.88 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
9.24 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/33450142/ |
1500 mg single, oral dose: 1500 mg route of administration: Oral experiment type: SINGLE co-administered: |
GEPOTIDACIN saliva | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
67% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
67% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
|
67% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/32429000/ |
750 mg single, intravenous dose: 750 mg route of administration: Intravenous experiment type: SINGLE co-administered: |
GEPOTIDACIN plasma | Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
major | weak (co-administration study) Comment: Itraconazole increased Cmax and AUCinf by 40% and 50%. Sources: https://pubmed.ncbi.nlm.nih.gov/33450142/ |
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minor | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no | ||||
no |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
The metabolism and disposition of GSK2140944 in healthy human subjects. | 2016 Aug |
|
In Vitro Activity of Gepotidacin, a Novel Triazaacenaphthylene Bacterial Topoisomerase Inhibitor, against a Broad Spectrum of Bacterial Pathogens. | 2016 Jan 4 |
|
Multicenter Investigation of Gepotidacin (GSK2140944) Agar Dilution Quality Control Determinations for Neisseria gonorrhoeae ATCC 49226. | 2016 Jul |
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Pharmacokinetic-Pharmacodynamic Evaluation of Gepotidacin against Gram-Positive Organisms Using Data from Murine Infection Models. | 2017 Feb |
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Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria. | 2017 Jul |
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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. | 2017 Jun |
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In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae. | 2017 Mar |
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In Vitro Activities of Gepotidacin (GSK2140944) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas. | 2017 Oct |
Patents
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/28373199
This phase 2, randomized, 2-part, multicenter, dose-ranging, response-adaptive study with optional intravenous-oral switch evaluated the efficacy and safety of gepotidacin for the treatment of Gram-positive acute bacterial skin and skin structure infections in 122 adult patients in the United States. The study had a double-blind phase (part 1; intravenous [750 mg or 1,000 mg every 12 h {q12h}]) and an open-label phase (part 2; intravenous [750 mg q12h, 1,000 mg q12h, or 1,000 q8h]). The primary endpoint was a composite of efficacy and safety which consisted of the early cure rate and the withdrawal rate due to drug-related adverse events and utilized a clinical utility index for dose selection. At the early efficacy visit (48 to 72 h after the first dose), the 750-mg q12h and 1,000-mg q8h groups met prespecified success criteria for clinical utility in terms of efficacy and safety; however, the 1,000-mg q12h group did not meet these criteria due to observed lower efficacy rates.
Route of Administration:
Intravenous
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26729499
The in vitro activities of gepotidacin were comparable against methicillin-susceptible and -resistant Staphylococcus aureus (MSSA and MRSA, respectively) isolates (MIC90, 0.5 μg/ml). The gepotidacin MIC90s were as follows (in micrograms per milliliter) for the indicated bacteria: Streptococcus pyogenes, 0.25; Escherichia coli, 2; Moraxella catarrhalis, ≤ 0.06; Streptococcus pneumoniae (0.25), Haemophilus influenzae, 1; Clostridium perfringens, 0.5; and Shigella spp., 1, including levofloxacin-resistant subsets.
Substance Class |
Chemical
Created
by
admin
on
Edited
Sat Dec 16 03:01:37 GMT 2023
by
admin
on
Sat Dec 16 03:01:37 GMT 2023
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Record UNII |
DVF0PR037D
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Record Status |
Validated (UNII)
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Record Version |
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DTXSID501028208
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Gepotidacin
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25101874
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CD-65
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C170025
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10050
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300000025811
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1075236-89-3
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CHEMBL3317856
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DVF0PR037D
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DB12134
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Related Record | Type | Details | ||
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SALT/SOLVATE -> PARENT |
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TARGET -> INHIBITOR |
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TARGET ORGANISM->INHIBITOR |
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SALT/SOLVATE -> PARENT |
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TARGET ORGANISM->INHIBITOR |
Targeted for drug resistant strains
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SALT/SOLVATE -> PARENT |
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Related Record | Type | Details | ||
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ACTIVE MOIETY |
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