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
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)
DescriptionSources: https://www.ncbi.nlm.nih.gov/pubmed/1330258Curator'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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/1330258
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
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL4550 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1330258 |
1.6 nM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Palliative | Unknown Approved UseUnknown |
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Sources: https://www.ncbi.nlm.nih.gov/pubmed/7759431 |
Palliative | Unknown Approved UseUnknown |
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Primary | Unknown Approved UseUnknown |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
15.81 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8033491 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
170 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8033491 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
12.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8033491 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8527269 |
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
Dose | Population | Adverse 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%) Sources: Page: p.61skin eruptions (16.7%) |
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
AE | Significance | Dose | Population |
---|---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/9041233
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/25025775
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.
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Classification Tree | Code System | Code | ||
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NCI_THESAURUS |
C1322
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7327
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136668-42-3
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60923
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9295C885I4
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C84130
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DTXSID20159882
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CHEMBL16596
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100000081103
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SUB10194MIG
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ACTIVE MOIETY
SALT/SOLVATE (PARENT)