QUIFLAPON

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 Search

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

Molecular Formula	C34H35ClN2O3S
Molecular Weight	587.171
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
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.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
5-lipoxygenase activating protein 7 Target ID: CHEMBL4550 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1330258	Inhibitor 8297		1.6 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Ulcerative colitis 123 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9041233	Palliative	Phase II 1132	Unknown Approved Use Unknown
Asthma 241 Sources: https://www.ncbi.nlm.nih.gov/pubmed/7759431	Palliative	Preclinical	Unknown Approved Use Unknown
Castration-resistant, bone-metastatic prostate cancer 2 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25875826	Primary	Basic research	Unknown Approved Use Unknown

C_max

Value	Dose	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	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

T_1/2

Value	Dose	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: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 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: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	Disc. AE: itching, skin eruptions... AEs leading to discontinuation/dose reduction: itching (16.7%) skin eruptions (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 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: https://pubmed.ncbi.nlm.nih.gov/8033491 Page: p.26	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8033491 Page: p.26	Disc. AE: Maculopapular rash... AEs leading to discontinuation/dose reduction: Maculopapular rash (16.7%) Sources: https://pubmed.ncbi.nlm.nih.gov/8033491 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: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 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: https://pubmed.ncbi.nlm.nih.gov/8527269 Page: p.61	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FASTED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8527269 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: https://pubmed.ncbi.nlm.nih.gov/8033491 Page: p.26	healthy, ADULT n = 6 Health Status: healthy Age Group: ADULT Sex: M Food Status: FED Population Size: 6 Sources: https://pubmed.ncbi.nlm.nih.gov/8033491 Page: p.26

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461 CYP1A2 1524

Drug as perpetrator

Target	Modality	Activity
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363678337	inconclusive [IC50 29.0929 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/432016#sid=103180027	inconclusive
CYP2C9 1819	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19739647/	yes [IC50 0.5 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19739647/	yes [IC50 11 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://pubmed.ncbi.nlm.nih.gov/19739647/	yes [IC50 5.8 uM]

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY111363	https://www.001chemical.com/chem/search?q=DY111363
1PlusChem LLC	1P0012NW	https://www.1pchem.com/search?query=1P0012NW
1PlusChem LLC	1P001EZX	https://www.1pchem.com/search?query=1P001EZX
AK Scientific	3856AH	https://aksci.com/item_detail.php?cat=3856AH
ApexBio Technology	A3609	https://www.apexbt.com/catalogsearch/result/?q=A3609
BLD Pharm	BD149985	http://www.bldpharm.com/search/Search.html?keyword=BD149985
BOC Sciences	136668-42-3	http://www.bocsci.com/description.asp?cas=136668-42-3
BOC Sciences	147030-01-1	http://www.bocsci.com/description.asp?cas=147030-01-1
Chem Scene	CS-0953	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0953
Matrix Scientific	145048	http://www.matrixscientific.com/145048.html
MedChem Express	HY-10037	https://www.medchemexpress.com/search.html?q=HY-10037&ft=&fa=&fp=
MolPort	MolPort-039-139-729	https://www.molport.com/shop/molecule-link/MolPort-039-139-729
MolPort	MolPort-044-724-555	https://www.molport.com/shop/molecule-link/MolPort-044-724-555
Molcore	MC111363	http://www.molcore.com/CatMC111363.html
Molnova	M11514	https://www.molnova.com/en/serch-list.html?keywords=M11514
Molnova	M12014	https://www.molnova.com/en/serch-list.html?keywords=M12014
MuseChem	I001412	https://www.musechem.com/product/I001412.html
MuseChem	I008941	https://www.musechem.com/product/I008941.html
ShangHai Biochempartner	BCP06574	http://www.biochempartner.com/search_BCP06574
Toronto Research Chemicals	C367338	https://www.trc-canada.com/product-detail/?CatNum=C367338
Toronto Research Chemicals	Q535400	https://www.trc-canada.com/product-detail/?CatNum=Q535400
eMolecules	300636138	https://orderbb.emolecules.com/search/#?query=300636138
eMolecules	43552138	https://orderbb.emolecules.com/search/#?query=43552138
eMolecules	43609260	https://orderbb.emolecules.com/search/#?query=43609260
eNovation Chemicals	D518761	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D518761&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-1222504436	https://mcule.com/MCULE-1222504436/
mcule	MCULE-4284165741	https://mcule.com/MCULE-4284165741/

PubMed

Title	Date	PubMed
Assessment of the in vivo biochemical efficacy of orally active leukotriene biosynthesis inhibitors.	1993 Sep	8147271
Role of 5-lipoxygenase products in the local accumulation of neutrophils in dermal inflammation in the rabbit.	1999 Sep 15	10477617

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 17:13:36 UTC 2023` Edited by `admin` on `Fri Dec 15 17:13:36 UTC 2023`
Record UNII	9295C885I4
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

QUIFLAPON

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