Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C26H26ClN2O3S2.Na |
| Molecular Weight | 537.069 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
[Na+].CN(C)C(=O)CCS[C@H](SCCC([O-])=O)C1=CC(\C=C\C2=NC3=CC(Cl)=CC=C3C=C2)=CC=C1
InChI
InChIKey=XNAYQOBPAXEYLI-LQKFMROPSA-M
InChI=1S/C26H27ClN2O3S2.Na/c1-29(2)24(30)12-14-33-26(34-15-13-25(31)32)20-5-3-4-18(16-20)6-10-22-11-8-19-7-9-21(27)17-23(19)28-22;/h3-11,16-17,26H,12-15H2,1-2H3,(H,31,32);/q;+1/p-1/b10-6+;/t26-;/m1./s1
| Molecular Formula | Na |
| Molecular Weight | 22.9898 |
| Charge | 1 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C26H26ClN2O3S2 |
| Molecular Weight | 514.079 |
| Charge | -1 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 1 / 1 |
| E/Z Centers | 1 |
| Optical Activity | UNSPECIFIED |
A potent, selective and orally active receptor antagonist of leukotriene D4, verlukast (MK-571), was discovered and developed from a styrylquinoline lead structure based on a hypothetical model of the leukotriene D4 receptor. MK-571 blocks the action of LTD4 in animals and man, and is effective in a number of animal models of antigen-induced bronchoconstriction at plasma concentration at or below 2 ug/mL. MK-571 also blocks antigen-induced asthmatic responses in man. MK-571 is a potent and selective leukotriene D4 (LTD4) antagonist and ABCC multidrug resistance protein 1(MRP1) inhibitor. The cysteinyl leukotrienes (CysLTs), LTC4, LTD4, and LTE4, mediate their actions through two distinct G-protein coupled receptors. LTD4 is the preferred ligand for the CysLT1 receptor, whereas LTC4 and LTD4 bind with approximately equal affinity to the CysLT2 receptor. MK-571 is a selective, orally active CysLT1 receptor antagonist. It blocks the binding of LTD4, but not LTC4, to human and guinea pig lung membranes with Ki values of 0.22 nM and 2.1 nM, respectively. MK-571 effectively blocks LTD4 activation of recombinant human and mouse CysLT1 receptors but is ineffective at blocking LTC4 or LTD4 activation of the recombinant human or murine CysLT2 receptors.
Originator
Sources: http://adisinsight.springer.com/drugs/800001553 | https://www.ncbi.nlm.nih.gov/pubmed/1793062
Curator's Comment: # Merck & Co
Approval Year
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effect of the leukotriene receptor antagonist MK-0679 on baseline pulmonary function in aspirin sensitive asthmatic subjects. | 1993 Dec |
|
| Characterization of the leukotriene D4 receptor in dimethylsulphoxide-differentiated U937 cells: comparison with the leukotriene D4 receptor in human lung and guinea-pig lung. | 1993 Feb 15 |
|
| Leukotriene D4-induced increases in cytosolic calcium in THP-1 cells: dependence on extracellular calcium and inhibition with selective leukotriene D4 receptor antagonists. | 1994 Jun |
|
| Adenosine triphosphate-dependent transport of anionic conjugates by the rabbit multidrug resistance-associated protein Mrp2 expressed in insect cells. | 1998 Jun |
|
| Overexpression of the multidrug resistance-associated protein (MRP1) in human heavy metal-selected tumor cells. | 1999 Jan 29 |
|
| Characterization of the human cysteinyl leukotriene CysLT1 receptor. | 1999 Jun 24 |
|
| Characterization of the human cysteinyl leukotriene 2 receptor. | 2000 Sep 29 |
|
| Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors. | 2001 Nov 1 |
|
| Functional analysis of ABCA8, a new drug transporter. | 2002 Oct 18 |
|
| Inverse agonist activity of selected ligands of the cysteinyl-leukotriene receptor 1. | 2004 Apr |
|
| Structural requirements for the flavonoid-mediated modulation of glutathione S-transferase P1-1 and GS-X pump activity in MCF7 breast cancer cells. | 2004 Apr 15 |
|
| Identification of multidrug resistance-associated protein 1 and glutathione as multidrug resistance mechanisms in human prostate cancer cells: chemosensitization with leukotriene D4 antagonists and buthionine sulfoximine. | 2004 Jun |
|
| Substrates and inhibitors of efflux proteins interfere with the MTT assay in cells and may lead to underestimation of drug toxicity. | 2004 Oct |
|
| The human multidrug-resistance-associated protein MRP1 mediates ATP-dependent transport of unconjugated bilirubin. | 2004 Oct 15 |
|
| Determination of the investigational anti-cancer drug 5,6-dimethylxanthenone-4-acetic acid and its acyl glucuronide in Caco-2 monolayers by liquid chromatography with fluorescence detection: application to transport studies. | 2004 Sep 25 |
|
| Endogenous thiols and MRP transporters contribute to Hg2+ efflux in HgCl2-treated tubular MDCK cells. | 2005 Jan 5 |
|
| Combined effects of GSTP1 and MRP1 in melanoma drug resistance. | 2005 Jul 25 |
|
| Modulatory effects of plant phenols on human multidrug-resistance proteins 1, 4 and 5 (ABCC1, 4 and 5). | 2005 Sep |
|
| Inhibition of MRP1-mediated efflux in human erythrocytes by mono-anionic bile salts. | 2005 Sep-Oct |
|
| Montelukast is a potent and durable inhibitor of multidrug resistance protein 2-mediated efflux of taxol and saquinavir. | 2009 Dec |
|
| Culture period-dependent change of function and expression of ATP-binding cassette transporters in Caco-2 cells. | 2009 Sep |
|
| Multidrug resistance protein transporter and Ins(1,4,5)P₃-sensitive Ca²+-signaling involved in adenosine triphosphate export via Gq protein-coupled NK₂-receptor stimulation with neurokinin A. | 2010 |
|
| MRP transporters as membrane machinery in the bradykinin-inducible export of ATP. | 2010 Apr |
|
| Chrysin blocks topotecan-induced apoptosis in Caco-2 cells in spite of inhibition of ABC-transporters. | 2010 Aug 15 |
|
| Interference with bile salt export pump function is a susceptibility factor for human liver injury in drug development. | 2010 Dec |
|
| Differential disposition of chenodeoxycholic acid versus taurocholic acid in response to acute troglitazone exposure in rat hepatocytes. | 2011 Apr |
|
| Multidrug resistance-associated protein 1 mediates 15-deoxy-Δ(12,14)-prostaglandin J2-induced expression of glutamate cysteine ligase expression via Nrf2 signaling in human breast cancer cells. | 2011 Aug 15 |
|
| Molecular characterization and functions of zebrafish ABCC2 in cellular efflux of heavy metals. | 2011 May |
|
| Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). | 2013 Dec |
|
| The role of efflux transporters on the transport of highly toxic aconitine, mesaconitine, hypaconitine, and their hydrolysates, as determined in cultured Caco-2 and transfected MDCKII cells. | 2013 Feb 4 |
|
| Transcellular transport of aconitine across human intestinal Caco-2 cells. | 2013 Jul |
|
| Arsenate accumulation and arsenate-induced glutathione export in astrocyte-rich primary cultures. | 2013 Jun |
|
| Multidrug resistance protein 1 (ABCC1) confers resistance to arsenic compounds in human myeloid leukemic HL-60 cells. | 2013 Jun |
|
| A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development. | 2013 Nov |
|
| Utilization of human nuclear receptors as an early counter screen for off-target activity: a case study with a compendium of 615 known drugs. | 2015 Jun |
|
| Nrf2 Regulates the Sensitivity of Mouse Keratinocytes to Nitrogen Mustard via Multidrug Resistance-Associated Protein 1 (Mrp1). | 2016 Jan |
Sample Use Guides
In a three-period, randomized, double-blind, crossover study, single doses of verlukast, 125 and 500 mg, and placebo were given intravenously by bolus infusion to nine patients with moderate, stable asthma (FEV1 40 to 80% predicted) on individual study days separated by a week.
Route of Administration:
Intravenous
Verlukast (5.8 x 10(-8)M) antagonized contractions of guinea pig trachea induced by LTC4 in the absence (dose ratio = 28) but not in the presence of 45 mM L-serine borate (dose ratio less than 2). L-660,711 (1.9 x 10(-5)M) did not block contractions of guinea pig trachea induced by histamine, acetylcholine, 5-hydroxytryptamine, PGF2 alpha, U-44069, or PGD2.
| Substance Class |
Chemical
Created
by
admin
on
Edited
Fri Dec 15 15:55:21 GMT 2023
by
admin
on
Fri Dec 15 15:55:21 GMT 2023
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| Record UNII |
Q8W8588793
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| Record Status |
Validated (UNII)
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| Record Version |
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