U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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
Structure of GEPOTIDACIN

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

HIDE SMILES / InChI

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
Unknown

Approved Use

Unknown
Curative
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 μg/mL
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
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
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
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
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
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
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
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
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
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
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
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

AUC

ValueDoseCo-administeredAnalytePopulation
15.9 μg × h/mL
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
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
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
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
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
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
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
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
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
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
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
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

T1/2

ValueDoseCo-administeredAnalytePopulation
9.07 h
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
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
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
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
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
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
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
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
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
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
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
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

Funbound

ValueDoseCo-administeredAnalytePopulation
67%
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%
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%
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

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
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
Pharmacokinetic-Pharmacodynamic Evaluation of Gepotidacin against Gram-Positive Organisms Using Data from Murine Infection Models.
2017 Feb
Gepotidacin (GSK2140944) In Vitro Activity against Gram-Positive and Gram-Negative Bacteria.
2017 Jul
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
In Vitro Activity of Gepotidacin (GSK2140944) against Neisseria gonorrhoeae.
2017 Mar
In Vitro Activities of Gepotidacin (GSK2140944) and Other Antimicrobial Agents against Human Mycoplasmas and Ureaplasmas.
2017 Oct
Patents

Sample Use Guides

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
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 Sat Dec 16 03:01:37 GMT 2023
Edited
by admin
on Sat Dec 16 03:01:37 GMT 2023
Record UNII
DVF0PR037D
Record Status Validated (UNII)
Record Version
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Name Type Language
GEPOTIDACIN
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
GEPOTIDACIN [USAN]
Common Name English
Gepotidacin [WHO-DD]
Common Name English
gepotidacin [INN]
Common Name English
GSK-2140944
Code English
GSK2140944
Code English
3H,8H-2A,5,8A-TRIAZAACENAPHTHYLENE-3,8-DIONE, 2-((4-(((3,4-DIHYDRO-2H-PYRANO(2,3-C)PYRIDIN-6-YL)METHYL)AMINO)-1-PIPERIDINYL)METHYL)-1,2-DIHYDRO-, (2R)-
Systematic Name English
Code System Code Type Description
EPA CompTox
DTXSID501028208
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
WIKIPEDIA
Gepotidacin
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
PUBCHEM
25101874
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
USAN
CD-65
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
NCI_THESAURUS
C170025
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
INN
10050
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
SMS_ID
300000025811
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
CAS
1075236-89-3
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
ChEMBL
CHEMBL3317856
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
FDA UNII
DVF0PR037D
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
DRUG BANK
DB12134
Created by admin on Sat Dec 16 03:01:37 GMT 2023 , Edited by admin on Sat Dec 16 03:01:37 GMT 2023
PRIMARY
Related Record Type Details
SALT/SOLVATE -> PARENT
TARGET -> INHIBITOR
TARGET ORGANISM->INHIBITOR
SALT/SOLVATE -> PARENT
TARGET ORGANISM->INHIBITOR
Targeted for drug resistant strains
SALT/SOLVATE -> PARENT
Related Record Type Details
ACTIVE MOIETY