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Identification
Name Pranlukast
Accession Number DB01411
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
ONO-RS 411
Salts Not Available
Brand names Not Available
Brand mixtures Not Available
Categories
  • Anti-Asthmatic Agents
  • Leukotriene Antagonists
CAS number 103177-37-3
Weight Average: 481.5026
Monoisotopic: 481.175004249
Chemical Formula C27H23N5O4
InChI Key InChIKey=UAJUXJSXCLUTNU-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)
Plain Text
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
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Chromones
Substructures
  • Phenols and Derivatives
  • Amino Ketones
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Chromones
  • Tetrazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Anisoles
  • Carboxamides and Derivatives
  • Imines
  • Benzoyl Derivatives
  • Cyanamides
  • Phenyl Esters
  • Benzamides
  • Anilines
Pharmacology
Indication Used as an adjunct to the standard therapy of inhaled steroids with inhaled long- and/or short-acting beta-agonists.
Pharmacodynamics Pranlukast is a cysteinyl leukotriene receptor-1 antagonist.
Mechanism of action Pranlukast 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.
Absorption Not Available
Volume of distribution Not Available
Protein binding Not Available
Metabolism Hepatic
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Side 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
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility 3.00e-03 g/l ALOGPS
logP 4.84 ALOGPS
logP 4.67 ChemAxon
logS -5.2 ALOGPS
pKa (strongest acidic) 5.96 ChemAxon
pKa (strongest basic) -2.2 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 119.09 ChemAxon
rotatable bond count 9 ChemAxon
refractivity 139.15 ChemAxon
polarizability 49.7 ChemAxon
References
Synthesis Reference Not Available
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
Resource Link
PubChem Compound 115100 Link_out
PubChem Substance 46508129 Link_out
ChemSpider 102999 Link_out
Therapeutic Targets Database DAP000977 Link_out
PharmGKB PA134698661 Link_out
Wikipedia http://en.wikipedia.org/wiki/Pranlukast Link_out
ATC Codes
  • R03DC02
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions Not Available
Targets

1. Cysteinyl leukotriene receptor 1

Pharmacological action: yes
Actions: antagonist

Receptor for cysteinyl leukotrienes mediating bronchoconstriction of individuals with and without asthma. Stimulation by LTD4 results in the contraction and proliferation of smooth muscle, edema, eosinophil migration and damage to the mucus layer in the lung. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. The rank order of affinities for the leukotrienes is LTD4 >> LTE4 = LTC4 >> LTB4

Organism class: human
UniProt ID: Q9Y271 Link_out
Gene: CYSLTR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other/unknown

Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. It is mainly secreted by macrophages and can induce cell death of certain tumor cell lines. It is potent pyrogen causing fever by direct action or by stimulation of interleukin 1 secretion and is implicated in the induction of cachexia, Under certain conditions it can stimulate cell proliferation and induce cell differentiation

Organism class: human
UniProt ID: P01375 Link_out
Gene: TNF Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: antagonist

Factor that induces terminal differentiation of late- developing B-cells to immunoglobulin secreting cells

Organism class: human
UniProt ID: P05113 Link_out
Gene: IL5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other/unknown

Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity

Organism class: human
UniProt ID: P12724 Link_out
Gene: RNASE3 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other/unknown

Appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins and generation of p50 by a cotranslational processing. The proteasome-mediated process ensures the production of both p50 and p105 and preserves their independent function, although processing of NFKB1/p105 also appears to occur posttranslationally. p50 binds to the kappa-B consensus sequence 5'-GGRNNYYCC-3', located in the enhancer region of genes involved in immune response and acute phase reactions. Plays a role in the regulation of apoptosis

Organism class: human
UniProt ID: P19838 Link_out
Gene: NFKB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Pharmacological action: unknown
Actions: other/unknown

Coats the epithelia of the intestines, airways, and other mucus membrane-containing organs. Thought to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces

Organism class: human
UniProt ID: Q02817 Link_out
Gene: MUC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S- warfarin, diclofenac, phenytoin, tolbutamide and losartan

UniProt ID: P11712 Link_out
Gene: CYP2C9
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

Actions: inhibitor

Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter

UniProt ID: Q92887 Link_out
Gene: ABCC2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Drug created on July 17, 2007 06:39 / Updated on February 08, 2013 16:20