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Details

Stereochemistry ACHIRAL
Molecular Formula C34H35ClN2O3S
Molecular Weight 587.171
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of QUIFLAPON

SMILES

CC(C)(C)SC1=C(CC(C)(C)C(O)=O)N(CC2=CC=C(Cl)C=C2)C3=C1C=C(OCC4=CC=C5C=CC=CC5=N4)C=C3

InChI

InChIKey=NZOONKHCNQFYCI-UHFFFAOYSA-N
InChI=1S/C34H35ClN2O3S/c1-33(2,3)41-31-27-18-26(40-21-25-15-12-23-8-6-7-9-28(23)36-25)16-17-29(27)37(20-22-10-13-24(35)14-11-22)30(31)19-34(4,5)32(38)39/h6-18H,19-21H2,1-5H3,(H,38,39)

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/25875826 https://www.ncbi.nlm.nih.gov/pubmed/8357985

Quiflapon Sodium (MK-0591; (3-[1-(4-chlorobenzyl)-3-(t-butylthio)-5-(quinolin-2-yl-methoxy)- indol-2-yl]-2,2-dimethyl propanoic acid, previously L-686,708) had been in phase II clinical studies for the treatment of inflammatory bowel disease, but the study was discontinued later, because in spite of MK-591 markedly inhibited Leukotrienes (LT) biosynthesis, it did not differ significantly from placebo in clinical efficacy. Also was discovered, that MK-0591 may modify the airway changes associated with bronchial hyper responsiveness, as well as offer symptomatic relief in asthma. MK-0591 is a selective and specific 5-Lipoxygenase-activating protein (FLAP) inhibitor with an IC50 value of 1.6 nM in a FLAP binding assay. In additional, recently was discovered, that MK591 possesses all major attributes of a standard anti-metastatic agent with significant cancer-selective effect, and suggest that MK591 may turn out to be an effective agent for therapy of castration-resistant, bone-metastatic prostate cancer. Though details of the molecular underpinnings of the anti-metastatic action of MK591 are unknown at this time, this finding gives an opportunity for further exploration to better understand the signaling mechanisms involved by in vitro and in vivo experiments.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.6 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Unknown

Approved Use

Unknown
Palliative
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
15.81 μg/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
6.9 μg/mL
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
5.93 μg/mL
125 mg 2 times / day multiple, oral
dose: 125 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.1 μg/mL
250 mg 1 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
170 μg × h/mL
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
39.93 μg × h/mL
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
65.9 μg × h/mL
125 mg 2 times / day multiple, oral
dose: 125 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
86.3 μg × h/mL
250 mg 1 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
12.2 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.74 h
250 mg 2 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.3 h
125 mg 2 times / day multiple, oral
dose: 125 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
9.2 h
250 mg 1 times / day multiple, oral
dose: 250 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
QUIFLAPON plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
500 mg single, oral
Highest studied dose
Dose: 500 mg
Route: oral
Route: single
Dose: 500 mg
Sources: Page: p.61
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.61
125 mg 2 times / day multiple, oral
Studied dose
Dose: 125 mg, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg, 2 times / day
Sources: Page: p.61
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.61
Disc. AE: itching, skin eruptions...
AEs leading to
discontinuation/dose reduction:
itching (16.7%)
skin eruptions (16.7%)
Sources: Page: p.61
250 mg 2 times / day multiple, oral
Studied dose
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.26
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FED
Population Size: 6
Sources: Page: p.26
Disc. AE: Maculopapular rash...
AEs leading to
discontinuation/dose reduction:
Maculopapular rash (16.7%)
Sources: Page: p.26
AEs

AEs

AESignificanceDosePopulation
itching 16.7%
Disc. AE
125 mg 2 times / day multiple, oral
Studied dose
Dose: 125 mg, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg, 2 times / day
Sources: Page: p.61
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.61
skin eruptions 16.7%
Disc. AE
125 mg 2 times / day multiple, oral
Studied dose
Dose: 125 mg, 2 times / day
Route: oral
Route: multiple
Dose: 125 mg, 2 times / day
Sources: Page: p.61
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FASTED
Population Size: 6
Sources: Page: p.61
Maculopapular rash 16.7%
Disc. AE
250 mg 2 times / day multiple, oral
Studied dose
Dose: 250 mg, 2 times / day
Route: oral
Route: multiple
Dose: 250 mg, 2 times / day
Sources: Page: p.26
healthy, ADULT
n = 6
Health Status: healthy
Age Group: ADULT
Sex: M
Food Status: FED
Population Size: 6
Sources: Page: p.26
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Assessment of the in vivo biochemical efficacy of orally active leukotriene biosynthesis inhibitors.
1993 Sep
Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit.
1999 Sep 15
Patents

Patents

Sample Use Guides

Patients received placebo or MK-591 (QUIFLAPON) at a dose of 12.5, 50, or 100 mg twice daily for 8 weeks
Route of Administration: Oral
The influence of MK591 (QUIFLAPON) on Toll-like Receptor (TLR-2 and -4) xpression was investigated by use of flow cytometry. RAW264.7 cells were pretreated with 25 µM MK591 followed by LPS (100 ng/ml) or Lipid A (100 ng/ml) stimulation. MK591 pretreatment attenuated significantly TLR-2 expression 4 hours post stimulation compared with vehicle pretreated cells.
Name Type Language
QUIFLAPON
INN  
INN  
Official Name English
quiflapon [INN]
Common Name English
3-(TERT-BUTYLTHIO)-1-(P-CHLOROBENZYL)-.ALPHA.,.ALPHA.-DIMETHYL-5-(2-QUINOLYLMETHOXY)INDOLE-2-PROPIONATE
Common Name English
1H-INDOLE-2-PROPANOIC ACID, 1-((4-CHLOROPHENYL)METHYL)-3-((1,1-DIMETHYLETHYL)THIO)-.ALPHA.,.ALPHA.-DIMETHYL-5-(2-QUINOLINYLMETHOXY)-
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C1322
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
Code System Code Type Description
INN
7327
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
CAS
136668-42-3
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
PUBCHEM
60923
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
FDA UNII
9295C885I4
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
NCI_THESAURUS
C84130
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
EPA CompTox
DTXSID20159882
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
ChEMBL
CHEMBL16596
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
SMS_ID
100000081103
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY
EVMPD
SUB10194MIG
Created by admin on Fri Dec 15 17:13:36 GMT 2023 , Edited by admin on Fri Dec 15 17:13:36 GMT 2023
PRIMARY