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Pranlukast

July 24, 2017
Common Name

Pranlukast Description

Pranlukast is only found in individuals that have used or taken this drug. It 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.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. Structure

MOLSDF3D-SDFPDBSMILESInChI View 3D Structure

Synonyms

Value Source ONO-RS 411HMDB

Chemical Formlia

C27H23N5O4 Average Molecliar Weight

481.5026 Monoisotopic Molecliar Weight

481.175004249 IUPAC Name

N-[4-oxo-2-(2H-1,2,3,4-tetrazol-5-yl)-4H-chromen-7-yl]-4-(4-phenylbutoxy)benzamide Traditional Name

pranlukast CAS Registry Number

103177-37-3 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

InChI Identifier

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)

InChI Key

UAJUXJSXCLUTNU-UHFFFAOYSA-N Chemical Taxonomy Description

This compound belongs to the class of chemical entities known as chromones. These are compounds containing a benzopyran-4-one moiety. Kingdom

Chemical entities Super Class

Organic compounds Class

Organoheterocyclic compounds Sub Class

Benzopyrans Direct Parent

Chromones Alternative Parents

  • Benzamides
  • Phenoxy compounds
  • Phenol ethers
  • Benzoyl derivatives
  • Pyranones and derivatives
  • Alkyl aryl ethers
  • Tetrazoles
  • Heteroaromatic compounds
  • Secondary carboxylic acid amides
  • Oxacyclic compounds
  • Azacyclic compounds
  • Organopnictogen compounds
  • Organonitrogen compounds
  • Organic oxides
  • Hydrocarbon derivatives

    • Substituents

  • Chromone
  • Benzamide
  • Benzoic acid or derivatives
  • Phenoxy compound
  • Benzoyl
  • Phenol ether
  • Alkyl aryl ether
  • Pyranone
  • Monocyclic benzene moiety
  • Benzenoid
  • Pyran
  • Azole
  • Heteroaromatic compound
  • Tetrazole
  • Carboxamide group
  • Secondary carboxylic acid amide
  • Oxacycle
  • Ether
  • Carboxylic acid derivative
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound

    • Molecliar Framework

    Aromatic heteropolycyclic compounds External Descriptors

    Not Available Ontology Status

    Expected but not Quantified Origin

  • Drug

    • Biofunction

  • Anti-Asthmatic Agents
  • Leukotriene Antagonists

    • Application

  • Pharmaceutical

    • Cellliar locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Physical Properties State

    Solid Experimental Properties

    Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility3.00e-03 g/LNot Available LogPNot AvailableNot Available

    Predicted Properties

    Property Value Source Water Solubility0.003 mg/mLALOGPS 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 Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

    Spectra Spectra

    Not Available Biological Properties Cellliar Locations

  • Cytoplasm
  • Extracellliar
  • Membrane

    • Biofluid Locations

  • Blood
  • Urine

    • Tissue Location

    Not Available Pathways

    Not Available Normal Concentrations

    Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01411

  • 21059682

    • details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01411

  • 21059682

    • details

    Abnormal Concentrations

    Not Available Associated Disorders and Diseases Disease References

    None Associated OMIM IDs

    None External Links DrugBank ID

    DB01411 DrugBank Metabolite ID

    Not Available Phenol Explorer Compound ID

    Not Available Phenol Explorer Metabolite ID

    Not Available FoodDB ID

    Not Available KNApSAcK ID

    Not Available Chemspider ID

    102999 KEGG Compound ID

    Not Available BioCyc ID

    Not Available BiGG ID

    Not Available Wikipedia Link

    Pranlukast NuGOwiki Link

    HMDB15481 Metagene Link

    HMDB15481 METLIN ID

    Not Available PubChem Compound

    115100 PDB ID

    Not Available ChEBI ID

    730485

    Product: Ademetionine

    References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References
    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:16702733 ]

    Enzymes

    General function:
    Involved in monooxygenase activity
    Specific function:
    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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
    Gene Name:
    CYP3A4
    Uniprot ID:
    P08684
    Molecular weight:
    57255.585
    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:19122337 ]
    General function:
    Involved in monooxygenase activity
    Specific function:
    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.
    Gene Name:
    CYP2C9
    Uniprot ID:
    P11712
    Molecular weight:
    55627.365
    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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
    General function:
    Involved in tumor necrosis factor receptor binding
    Specific function:
    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
    Gene Name:
    TNF
    Uniprot ID:
    P01375
    Molecular weight:
    25644.1
    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:12801315 ]
    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:12801316 ]
    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:17430359 ]
    General function:
    Involved in protein binding
    Specific function:
    NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52 and the heterodimeric p65-p50 complex appears to be most abundant one. The dimers bind at kappa-B sites in the DNA of their target genes and the individual dimers have distinct preferences for different kappa-B sites that they can bind with distinguishable affinity and specificity. Different dimer combinations act as transcriptional activators or repressors, respectively. NF-kappa-B is controlled by various mechanisms of post-translational modification and subcellular compartmentalization as well as by interactions with other cofactors or corepressors. NF-kappa-B complexes are held in the cytoplasm in an inactive state complexed with members of the NF- kappa-B inhibitor (I-kappa-B) family. In a conventional activation pathway, I-kappa-B is phosphorylated by I-kappa-B kinases (IKKs) in response to different activators, subsequently degraded thus liberating the active NF-kappa-B complex which translocates to the nucleus. NF-kappa-B heterodimeric p65-p50 and RelB-p50 complexes are transcriptional activators. The NF-kappa-B p50-p50 homodimer is a transcriptional repressor, but can act as a transcriptional activator when associated with BCL3. NFKB1 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p105 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 post- translationally. 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. In a complex with MAP3K8, NFKB1/p105 represses MAP3K8-induced MAPK signaling; active MAP3K8 is released by proteasome-dependent degradation of NFKB1/p105
    Gene Name:
    NFKB1
    Uniprot ID:
    P19838
    Molecular weight:
    105355.2
    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:12801315 ]
    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:12801316 ]
    General function:
    Involved in G-protein coupled receptor protein signaling pathway
    Specific function:
    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
    Gene Name:
    CYSLTR1
    Uniprot ID:
    Q9Y271
    Molecular weight:
    38540.5
    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:11264758 ]
    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:11854273 ]
    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:15475658 ]
    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:16864492 ]
    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:17112405 ]
    6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
    General function:
    Not Available
    Specific function:
    Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity
    Gene Name:
    RNASE3
    Uniprot ID:
    P12724
    Molecular weight:
    18386.0
    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:10028377 ]
    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:10804983 ]
    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:11476469 ]
    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:15136379 ]
    General function:
    Not Available
    Specific function:
    Factor that induces terminal differentiation of late- developing B-cells to immunoglobulin secreting cells
    Gene Name:
    IL5
    Uniprot ID:
    P05113
    Molecular weight:
    15238.0
    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:10773010 ]
    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:11972613 ]
    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:12692940 ]
    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:15650315 ]
    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:16892782 ]

    Transporters

    General function:
    Involved in ATP binding
    Specific function:
    Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
    Gene Name:
    ABCC2
    Uniprot ID:
    Q92887
    Molecular weight:
    174205.6
    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:15618649 ]

    PMID: 8762063

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