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Details

Stereochemistry ACHIRAL
Molecular Formula C18H12ClF3N4O4
Molecular Weight 440.7611
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DELAFLOXACIN

SMILES

c1c2c(c(c(c1F)N3CC(C3)O)Cl)n(cc(c2=O)C(=O)O)-c4c(cc(c(=N)[nH]4)F)F

InChI

InChIKey=DYDCPNMLZGFQTM-UHFFFAOYSA-N
InChI=1S/C18H12ClF3N4O4/c19-12-13-7(1-9(20)14(12)25-3-6(27)4-25)15(28)8(18(29)30)5-26(13)17-11(22)2-10(21)16(23)24-17/h1-2,5-6,27H,3-4H2,(H2,23,24)(H,29,30)

HIDE SMILES / InChI

Molecular Formula C18H12ClF3N4O4
Molecular Weight 440.7611
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: http://www.malinplc.com/wp-content/uploads/2015/10/Melinta-Therapeutics-Presents-Complete-Delafloxacin-Results-09.10.15.pdf

Delafloxacin (CAS registry number 189279-58-1) was described as WQ-3034 by Wakunaga Pharmaceutical Co., Ltd., Osaka & Hiroshima, Japan. It was first licensed in 1999 to Abbott Park, IL, and further developed as ABT-492. Delafloxacin (Baxdela), a fluoroquinolone antibiotic, is currently being developed by Melinta Therapeutics. It is a novel investigational fluoroquinolone in development for the treatment of uncomplicated gonorrhea, and acute bacterial skin and skin structure infections. Delafloxacin shows MICs remarkably low against Gram-positive organisms and anaerobes and similar to those of ciprofloxacin against Gram-negative bacteria. It remains active against most fluoroquinolone-resistant strains, except enterococci. Its potency is further increased in acidic environments (found in many infection sites). Delafloxacin is active on staphylococci growing intracellularly or in biofilms. Delafloxacin is a dual-targeting fluoroquinolone, capable of forming cleavable complexes with DNA and topoisomerase IV or DNA gyrase and of inhibiting the activity of these enzymes in both Gram-positive and Gram-negative bacteria. On Oct 24, 2016, Melinta Therapeutics Submitted Baxdela New Drug Application for hospital-treated skin infections.

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
BAXDELA

Approved Use

BAXDELA is a fluoroquinolone antibacterial indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (1.1) To reduce the development of drug-resistant bacteria and maintain the effectiveness of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.2)

Launch Date

1497744000000
Curative
BAXDELA

Approved Use

BAXDELA is a fluoroquinolone antibacterial indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (1.1) To reduce the development of drug-resistant bacteria and maintain the effectiveness of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.2)

Launch Date

1497744000000
Curative
BAXDELA

Approved Use

BAXDELA is a fluoroquinolone antibacterial indicated in adults for the treatment of acute bacterial skin and skin structure infections (ABSSSI) caused by designated susceptible bacteria. (1.1) To reduce the development of drug-resistant bacteria and maintain the effectiveness of BAXDELA and other antibacterial drugs, BAXDELA should be used only to treat infections that are proven or strongly suspected to be caused by bacteria. (1.2)

Launch Date

1497744000000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
8.94 μg/mL
300 mg single, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
7.17 μg/mL
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
9.29 μg/mL
300 mg 2 times / day steady-state, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
7.45 μg/mL
450 mg 2 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
21.8 μg × h/mL
300 mg single, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
22.7 μg × h/mL
450 mg single, oral
dose: 450 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
23.4 μg × h/mL
300 mg 2 times / day steady-state, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: STEADY-STATE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
30.8 μg × h/mL
450 mg 2 times / day steady-state, oral
dose: 450 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
3.7 h
300 mg single, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
16%
300 mg single, intravenous
dose: 300 mg
route of administration: Intravenous
experiment type: SINGLE
co-administered:
DELAFLOXACIN MEGLUMINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Other AEs: Nausea, Gastrointestinal disorders...
Other AEs:
Nausea (50%)
Gastrointestinal disorders (87.5%)
Vomiting (75%)
Diarrhea (25%)
Retching (12.5%)
Nervous system disorders (12.5%)
Dizziness (12.5%)
Feeling hot (12.5%)
Respiratory, thoracic and mediastinal disorders (12.5%)
Rhinorrhea (12.5%)
Skin and subcutaneous tissue disorders (12.5%)
Pruritus
Sources:
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy, adult
Disc. AE: Tendinitis, Tendon rupture...
AEs leading to
discontinuation/dose reduction:
Tendinitis (serious)
Tendon rupture (serious)
Peripheral neuropathy (serious)
Myasthenia gravis (serious)
Sources:
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy
Disc. AE: Hypersensitivity...
AEs leading to
discontinuation/dose reduction:
Hypersensitivity (0.1%)
Sources:
300 |450 mg|mg 2 times / day multiple, intravenous|oral
Recommended
Dose: 300 |450 mg|mg, 2 times / day
Route: intravenous|oral
Route: multiple
Dose: 300 |450 mg|mg, 2 times / day
Sources:
unhealthy
Disc. AE: Vomiting, Hypersensitivity...
AEs leading to
discontinuation/dose reduction:
Vomiting (0.1%)
Hypersensitivity (0.1%)
Urticaria (0.3%)
Dermatitis allergic (0.1%)
Sources:
AEs

AEs

AESignificanceDosePopulation
Pruritus
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Dizziness 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Feeling hot 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Nervous system disorders 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Respiratory, thoracic and mediastinal disorders 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Retching 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Rhinorrhea 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Skin and subcutaneous tissue disorders 12.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Diarrhea 25%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Nausea 50%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Vomiting 75%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Gastrointestinal disorders 87.5%
1200 mg single, intravenous
Highest studied dose
Dose: 1200 mg
Route: intravenous
Route: single
Dose: 1200 mg
Sources:
healthy, 19- 64 years
Health Status: healthy
Age Group: 19- 64 years
Sex: M+F
Sources:
Myasthenia gravis serious
Disc. AE
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy, adult
Peripheral neuropathy serious
Disc. AE
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy, adult
Tendinitis serious
Disc. AE
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy, adult
Tendon rupture serious
Disc. AE
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy, adult
Hypersensitivity 0.1%
Disc. AE
300 mg 2 times / day multiple, intravenous
Recommended
Dose: 300 mg, 2 times / day
Route: intravenous
Route: multiple
Dose: 300 mg, 2 times / day
Sources:
unhealthy
Dermatitis allergic 0.1%
Disc. AE
300 |450 mg|mg 2 times / day multiple, intravenous|oral
Recommended
Dose: 300 |450 mg|mg, 2 times / day
Route: intravenous|oral
Route: multiple
Dose: 300 |450 mg|mg, 2 times / day
Sources:
unhealthy
Hypersensitivity 0.1%
Disc. AE
300 |450 mg|mg 2 times / day multiple, intravenous|oral
Recommended
Dose: 300 |450 mg|mg, 2 times / day
Route: intravenous|oral
Route: multiple
Dose: 300 |450 mg|mg, 2 times / day
Sources:
unhealthy
Vomiting 0.1%
Disc. AE
300 |450 mg|mg 2 times / day multiple, intravenous|oral
Recommended
Dose: 300 |450 mg|mg, 2 times / day
Route: intravenous|oral
Route: multiple
Dose: 300 |450 mg|mg, 2 times / day
Sources:
unhealthy
Urticaria 0.3%
Disc. AE
300 |450 mg|mg 2 times / day multiple, intravenous|oral
Recommended
Dose: 300 |450 mg|mg, 2 times / day
Route: intravenous|oral
Route: multiple
Dose: 300 |450 mg|mg, 2 times / day
Sources:
unhealthy
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
no (co-administration study)
Comment: An in vivo DDI study (Study ML-3341-118) of multiple oral doses of delafloxacin (450 mg Q12h) on a single oral dose of midazolam (5 mg) demonstrated no impact on midazolam PK, and minimal impact on 1-hydroxymidazolam PK
Page: 16
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
no
no
no
no
no
no
yes
yes
yes
no (co-administration study)
Comment: Delafloxacin AUC0-24 values from patients who received P-gp/BCRP inhibitors along with delafloxacin are overlayed with the values from patients who received no P-gp/BCRP inhibitors.
Page: 37
yes
no (co-administration study)
Comment: Delafloxacin AUC0-24 values from patients who received P-gp/BCRP inhibitors along with delafloxacin are overlayed with the values from patients who received no P-gp/BCRP inhibitors.
Page: 37
yes
yes (pharmacogenomic study)
Comment: The Cmin data from Study M00-224 seems significantly correlated with UGT2B15*2 genotype. Due to the small sample size (N=27), Applicant concluded that further confirmation is required to elucidate the role of UGT2B15.
Page: 15
Tox targets

Tox targets

PubMed

PubMed

TitleDatePubMed
Comparative antimicrobial activities of the newly synthesized quinolone WQ-3034, levofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis and Mycobacterium avium complex.
2000 Feb
New antibiotics for antibiotic-resistant bacteria.
2009 May 28
Methicillin-resistant Staphylococcus aureus: a pervasive pathogen highlights the need for new antimicrobial development.
2010 Dec
Patents

Sample Use Guides

900mg orally (2 x 450 mg tablets) administered once
Route of Administration: Oral
Delafloxacin demonstrated potent in vitro activity against this set of Staphylococcus aureus (MRSA) isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively.
Substance Class Chemical
Created
by admin
on Sat Jun 26 13:49:56 UTC 2021
Edited
by admin
on Sat Jun 26 13:49:56 UTC 2021
Record UNII
6315412YVF
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
DELAFLOXACIN
INN   USAN   WHO-DD  
USAN   INN  
Official Name English
DELAFLOXACIN [MI]
Common Name English
DELAFLOXACIN [INN]
Common Name English
RX-3341
Code English
ABT-492
Code English
WQ-3034
Code English
DELAFLOXACIN [WHO-DD]
Common Name English
3-QUINOLINECARBOXYLIC ACID, 1-(6-AMINO-3,5-DIFLUORO-2-PYRIDINYL)-8-CHLORO-6-FLUORO-1,4-DIHYDRO-7-(3-HYDROXY-1-AZETIDINYL)-4-OXO-
Common Name English
DELAFLOXACIN [USAN]
Common Name English
BAXDELA
Brand Name English
1-(6-AMINO-3,5-DIFLUOROPYRIDIN-2-YL)-8-CHLORO-6-FLUORO-7-(3-HYDROXYAZETIDIN-1-YL)-4-OXO-1,4-DIHYDROQUINOLINE-3-CARBOXYLIC ACID
Systematic Name English
Classification Tree Code System Code
NDF-RT N0000193223
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
WHO-ATC J01MA23
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
NCI_THESAURUS C795
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
Code System Code Type Description
INN
9064
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
PUBCHEM
487101
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
ChEMBL
CHEMBL2105637
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
MERCK INDEX
M12032
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
RXCUI
1927663
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
DRUG BANK
DB11943
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
CAS
189279-58-1
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
LACTMED
Delafloxacin
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
DRUG CENTRAL
5238
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
FDA UNII
6315412YVF
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
NCI_THESAURUS
C87390
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
EPA CompTox
189279-58-1
Created by admin on Sat Jun 26 13:49:56 UTC 2021 , Edited by admin on Sat Jun 26 13:49:56 UTC 2021
PRIMARY
Related Record Type Details
EXCRETED UNCHANGED
Following a single oral dose of 14C-labeled delafloxacin, 50% of the radioactivity is excreted in urine as unchanged delafloxacin and glucuronide metabolites and 48% is excreted in feces as unchanged delafloxacin.
FECAL; URINE
TRANSPORTER -> SUBSTRATE
TRANSPORTER -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> INDUCER
Delafloxacin was a mild inducer (less than 2 fold) of CYP3A4 at a clinically relevant concentration.
METABOLIC ENZYME -> SUBSTRATE
EXCRETED UNCHANGED
After single intravenous dose of 14C-labeled delafloxacin, 65% of the radioactivity is excreted in urine as unchanged delafloxacin and glucuronide metabolites and 28% is excreted in feces as unchanged delafloxacin.
FECAL; URINE
BINDER->LIGAND
BINDING
METABOLIC ENZYME -> SUBSTRATE
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> INDUCER
Delafloxacin was a mild inducer (less than 2 fold) of CYP2C9 at a concentration of 100 ?M
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC MULTIPLE ORAL ADMINISTRATION

Tmax PHARMACOKINETIC FASTED CONDITION

ORAL ADMINISTRATION

NOAEL TOXICITY ORGAN SYSTEM OR TYPE OF EFFECT
TOXICITY
SPECIES
TOXICITY
ROUTE OF ADMINISTRATION
TOXICITY
COMMENTS

Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

SINGLE DOSE