You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NamePranlukast
Accession NumberDB01411
TypeSmall Molecule
GroupsApproved
Description

Pranlukast is a cysteinyl leukotriene receptor-1 antagonist. It antagonizes or reduces bronchospasm caused, principally in asthmatics, by an allergic reaction to accidentally or inadvertently encountered allergens.

Structure
Thumb
Synonyms
SynonymLanguageCode
ONO-RS 411Not AvailableNot Available
SID50126316Not AvailableNot Available
SaltsNot Available
Brand namesNot Available
Brand mixturesNot Available
Categories
CAS number103177-37-3
WeightAverage: 481.5026
Monoisotopic: 481.175004249
Chemical FormulaC27H23N5O4
InChI KeyUAJUXJSXCLUTNU-UHFFFAOYSA-N
InChI
InChI=1S/C27H23N5O4/c33-23-17-25(26-29-31-32-30-26)36-24-16-20(11-14-22(23)24)28-27(34)19-9-12-21(13-10-19)35-15-5-4-8-18-6-2-1-3-7-18/h1-3,6-7,9-14,16-17H,4-5,8,15H2,(H,28,34)(H,29,30,31,32)
IUPAC Name
N-[4-oxo-2-(2H-1,2,3,4-tetrazol-5-yl)-4H-chromen-7-yl]-4-(4-phenylbutoxy)benzamide
SMILES
O=C(NC1=CC2=C(C=C1)C(=O)C=C(O2)C1=NNN=N1)C1=CC=C(OCCCCC2=CC=CC=C2)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzopyrans
SubclassChromones
Direct parentChromones
Alternative parentsAnilides; Benzamides; Phenol Ethers; Benzoyl Derivatives; Pyranones and Derivatives; Alkyl Aryl Ethers; Tetrazoles; Secondary Carboxylic Acid Amides; Polyamines; Carboxylic Acids; Enolates
Substituentsbenzamide; phenol ether; benzoyl; alkyl aryl ether; pyranone; pyran; benzene; tetrazole; azole; secondary carboxylic acid amide; carboxamide group; carboxylic acid; ether; polyamine; enolate; carboxylic acid derivative; amine; organonitrogen compound
Classification descriptionThis compound belongs to the chromones. These are compounds containing a benzopyran-4-one moiety.
Pharmacology
IndicationUsed as an adjunct to the standard therapy of inhaled steroids with inhaled long- and/or short-acting beta-agonists.
PharmacodynamicsPranlukast is a cysteinyl leukotriene receptor-1 antagonist.
Mechanism of actionPranlukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Pranlukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicitySide effects include headache, abdominal or stomach pain, cough, dental pain, dizziness, fever, heartburn, skin rash, stuffy nose, weakness or unusual tiredness.
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.991
Blood Brain Barrier + 0.9446
Caco-2 permeable - 0.6689
P-glycoprotein substrate Non-substrate 0.5976
P-glycoprotein inhibitor I Non-inhibitor 0.719
P-glycoprotein inhibitor II Non-inhibitor 0.6885
Renal organic cation transporter Non-inhibitor 0.8511
CYP450 2C9 substrate Non-substrate 0.8643
CYP450 2D6 substrate Non-substrate 0.8403
CYP450 3A4 substrate Non-substrate 0.5077
CYP450 1A2 substrate Non-inhibitor 0.7009
CYP450 2C9 substrate Non-inhibitor 0.5597
CYP450 2D6 substrate Non-inhibitor 0.8714
CYP450 2C19 substrate Non-inhibitor 0.5194
CYP450 3A4 substrate Non-inhibitor 0.5679
CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6646
Ames test AMES toxic 0.5986
Carcinogenicity Non-carcinogens 0.875
Biodegradation Not ready biodegradable 0.997
Rat acute toxicity 2.2158 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.7439
hERG inhibition (predictor II) Non-inhibitor 0.7501
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.003ALOGPS
logP4.84ALOGPS
logP4.67ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)5.96ChemAxon
pKa (Strongest Basic)-2.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area119.09 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity139.15 m3·mol-1ChemAxon
Polarizability49.7 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Seiei Sasatani, Masashi Shiota, Yoshinori Ii, “Granules containing pranlukast, process for producing the granules, and method of improving adhesiveness of pranlukast.” U.S. Patent US5876760, issued March, 1995.

US5876760
General Reference
  1. Nakade S, Ueda S, Ohno T, Nakayama K, Miyata Y, Yukawa E, Higuchi S: Population pharmacokinetics of pranlukast hydrate dry syrup in children with allergic rhinitis and bronchial asthma. Drug Metab Pharmacokinet. 2006 Apr;21(2):133-9. Pubmed
External Links
ResourceLink
PubChem Compound115100
PubChem Substance46508129
ChemSpider102999
Therapeutic Targets DatabaseDAP000977
PharmGKBPA134698661
WikipediaPranlukast
ATC CodesR03DC02
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Cysteinyl leukotriene receptor 1

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: antagonist

Components

Name UniProt ID Details
Cysteinyl leukotriene receptor 1 Q9Y271 Details

References:

  1. Yoo SH, Park SH, Song JS, Kang KH, Park CS, Yoo JH, Choi BW, Hahn MH: Clinical effects of pranlukast, an oral leukotriene receptor antagonist, in mild-to-moderate asthma: a 4 week randomized multicentre controlled trial. Respirology. 2001 Mar;6(1):15-21. Pubmed
  2. Ogasawara H, Ishii S, Yokomizo T, Kakinuma T, Komine M, Tamaki K, Shimizu T, Izumi T: Characterization of mouse cysteinyl leukotriene receptors mCysLT1 and mCysLT2: differential pharmacological properties and tissue distribution. J Biol Chem. 2002 May 24;277(21):18763-8. Epub 2002 Feb 19. Pubmed
  3. Ishinaga H, Takeuchi K, Kishioka C, Suzuki S, Basbaum C, Majima Y: Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells. Pharmacology. 2005 Feb;73(2):89-96. Epub 2004 Oct 5. Pubmed
  4. Shirasaki H, Kanaizumi E, Seki N, Kikuchi M, Watanabe K, Konno N, Himi T: Distribution of specific binding sites for cysteinyl leukotriene 1 receptor antagonist in human nasal mucosa. Acta Otolaryngol. 2006 Sep;126(9):948-51. Pubmed
  5. Ding Q, Wei EQ, Zhang YJ, Zhang WP, Chen Z: Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice. Acta Pharmacol Sin. 2006 Dec;27(12):1526-36. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Tumor necrosis factor

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Tumor necrosis factor P01375 Details

References:

  1. Tomari S, Matsuse H, Machida I, Kondo Y, Kawano T, Obase Y, Fukushima C, Shimoda T, Kohno S: Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics. Clin Exp Allergy. 2003 Jun;33(6):795-801. Pubmed
  2. Ichiyama T, Hasegawa S, Umeda M, Terai K, Matsubara T, Furukawa S: Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T cells. Clin Exp Allergy. 2003 Jun;33(6):802-7. Pubmed
  3. Ichiyama T, Kajimoto M, Hasegawa M, Hashimoto K, Matsubara T, Furukawa S: Cysteinyl leukotrienes enhance tumour necrosis factor-alpha-induced matrix metalloproteinase-9 in human monocytes/macrophages. Clin Exp Allergy. 2007 Apr;37(4):608-14. Pubmed

3. Interleukin-5

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Interleukin-5 P05113 Details

References:

  1. Hojo M, Suzuki M, Maghni K, Hamid Q, Powell WS, Martin JG: Role of cysteinyl leukotrienes in CD4 T cell-driven late allergic airway responses. J Pharmacol Exp Ther. 2000 May;293(2):410-6. Pubmed
  2. Nabe T, Yamashita K, Miura M, Kawai T, Kohno S: Cysteinyl leukotriene-dependent interleukin-5 production leading to eosinophilia during late asthmatic response in guinea-pigs. Clin Exp Allergy. 2002 Apr;32(4):633-40. Pubmed
  3. Nogimura M, Nagata M, Sutani A, Saito K, Sakamoto Y: [Study on the effect of cysteinyl leukotriene antagonist, pranlukast hydrate, on adhesive interaction between eosinophils and pulmonary endothelial cells] Nihon Kokyuki Gakkai Zasshi. 2002 Dec;40(12):919-24. Pubmed
  4. Fukushima C, Matsuse H, Hishikawa Y, Kondo Y, Machida I, Saeki S, Kawano T, Tomari S, Obase Y, Shimoda T, Koji T, Kohno S: Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism. Int Arch Allergy Immunol. 2005 Feb;136(2):165-72. Epub 2005 Jan 12. Pubmed
  5. Matsuse H, Kondo Y, Machida I, Kawano T, Saeki S, Tomari S, Obase Y, Fukushima C, Mizuta Y, Kohno S: Effects of anti-inflammatory therapies on recurrent and low-grade respiratory syncytial virus infections in a murine model of asthma. Ann Allergy Asthma Immunol. 2006 Jul;97(1):55-60. Pubmed

4. Eosinophil cationic protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Eosinophil cationic protein P12724 Details

References:

  1. Horiguchi T, Tachikawa S, Kasahara J, Doi M, Shiga M: Effects of pranlukast hydrate on serum eosinophil cationic protein levels in patients with adult bronchial asthma. Arzneimittelforschung. 1999 Jan;49(1):35-7. Pubmed
  2. Ishioka S, Hozawa S, Haruta Y, Hiyama K, Maeda A, Yamakido M: Pranlukast, a cysteinyl leukotriene antagonist, reduces serum eosinophil cationic protein levels in patients with asthma. Hiroshima J Med Sci. 1999 Dec;48(4):105-10. Pubmed
  3. Obase Y, Shimoda T, Tomari S, Mitsuta K, Fukushima C, Kawano T, Matsuse H, Kohno S: Effects of pranlukast on aspirin-induced bronchoconstriction: differences in chemical mediators between aspirin-intolerant and tolerant asthmatic patients. Ann Allergy Asthma Immunol. 2001 Jul;87(1):74-9. Pubmed
  4. Kanazawa H, Yoshikawa T, Hirata K, Yoshikawa J: Effects of pranlukast administration on vascular endothelial growth factor levels in asthmatic patients. Chest. 2004 May;125(5):1700-5. Pubmed

5. Nuclear factor NF-kappa-B p105 subunit

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Nuclear factor NF-kappa-B p105 subunit P19838 Details

References:

  1. Tomari S, Matsuse H, Machida I, Kondo Y, Kawano T, Obase Y, Fukushima C, Shimoda T, Kohno S: Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics. Clin Exp Allergy. 2003 Jun;33(6):795-801. Pubmed
  2. Ichiyama T, Hasegawa S, Umeda M, Terai K, Matsubara T, Furukawa S: Pranlukast inhibits NF-kappa B activation in human monocytes/macrophages and T cells. Clin Exp Allergy. 2003 Jun;33(6):802-7. Pubmed

6. Mucin-2

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: other/unknown

Components

Name UniProt ID Details
Mucin-2 Q02817 Details

References:

  1. Ishinaga H, Takeuchi K, Kishioka C, Suzuki S, Basbaum C, Majima Y: Pranlukast inhibits NF-kappaB activation and MUC2 gene expression in cultured human epithelial cells. Pharmacology. 2005 Feb;73(2):89-96. Epub 2004 Oct 5. Pubmed
  2. Bai CH, Song SY, Kim YD: The inhibitory effect of the leukotriene receptor antagonist on leukotriene D4-induced MUC2/5AC gene expression and mucin secretion in human airway epithelial cells. Auris Nasus Larynx. 2007 Jun;34(2):203-6. Epub 2007 Jan 12. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Nakade S, Yamauchi A, Komaba J, Ohno T, Kitagawa J, Honda N, Hasegawa C, Yoneda K, Kodama Y, Yasuda K, Azuma J, Miyata Y: Effect of clarithromycin on the pharmacokinetics of pranlukast in healthy volunteers. Drug Metab Pharmacokinet. 2008;23(6):428-33. Pubmed

2. Cytochrome P450 2C9

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Cytochrome P450 2C9 P11712 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters

1. Canalicular multispecific organic anion transporter 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Canalicular multispecific organic anion transporter 1 Q92887 Details

References:

  1. Horikawa M, Kato Y, Tyson CA, Sugiyama Y: The potential for an interaction between MRP2 (ABCC2) and various therapeutic agents: probenecid as a candidate inhibitor of the biliary excretion of irinotecan metabolites. Drug Metab Pharmacokinet. 2002;17(1):23-33. Pubmed

Comments
comments powered by Disqus
Drug created on July 17, 2007 06:39 / Updated on September 16, 2013 17:14