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Details

Stereochemistry ACHIRAL
Molecular Formula C34H34ClN2O3S.Na
Molecular Weight 609.153
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of QUIFLAPON SODIUM

SMILES

[Na+].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=YPURUCMVRRNPHJ-UHFFFAOYSA-M
InChI=1S/C34H35ClN2O3S.Na/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);/q;+1/p-1

HIDE SMILES / InChI

Description

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.

Originator

Approval Year

Targets

Primary TargetPharmacologyConditionPotency
1.6 nM [IC50]

Conditions

ConditionModalityTargetsHighest PhaseProduct
Palliative
Unknown
Palliative
Unknown
Primary
Unknown

Cmax

ValueDoseCo-administeredAnalytePopulation
6.9 μg/mL
250 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
8.1 μg/mL
250 mg 1 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
15.81 μg/mL
500 mg single, oral
QUIFLAPON plasma
Homo sapiens
5.93 μg/mL
125 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens

AUC

ValueDoseCo-administeredAnalytePopulation
39.93 μg × h/mL
250 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
86.3 μg × h/mL
250 mg 1 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
170 μg × h/mL
500 mg single, oral
QUIFLAPON plasma
Homo sapiens
65.9 μg × h/mL
125 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens

T1/2

ValueDoseCo-administeredAnalytePopulation
5.74 h
250 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
9.2 h
250 mg 1 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens
12.2 h
500 mg single, oral
QUIFLAPON plasma
Homo sapiens
8.3 h
125 mg 2 times / day multiple, oral
QUIFLAPON plasma
Homo sapiens

Doses

AEs

Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as perpetrator​

PubMed

Patents

Sample Use Guides

In Vivo Use Guide
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
In Vitro Use Guide
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.