Identification

Name
Pranlukast
Accession Number
DB01411
Type
Small Molecule
Groups
Approved, Investigational
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
  • ONO-RS 411
External IDs
CCN 00401 / CCN-00401 / ONO 1078 / ONO-1078 / RS 411 / RS-411 / SB 205312 / SB-205312
Categories
UNII
TB8Z891092
CAS number
103177-37-3
Weight
Average: 481.512
Monoisotopic: 481.175004241
Chemical Formula
C27H23N5O4
InChI Key
NBQKINXMPLXUET-UHFFFAOYSA-N
InChI
InChI=1S/C27H23N5O4/c33-23-17-24(26-29-31-32-30-26)36-25-21(23)10-6-11-22(25)28-27(34)19-12-14-20(15-13-19)35-16-5-4-9-18-7-2-1-3-8-18/h1-3,6-8,10-15,17H,4-5,9,16H2,(H,28,34)(H,29,30,31,32)
IUPAC Name
N-[4-oxo-2-(2H-1,2,3,4-tetrazol-5-yl)-4H-chromen-8-yl]-4-(4-phenylbutoxy)benzamide
SMILES
O=C(NC1=C2OC(=CC(=O)C2=CC=C1)C1=NNN=N1)C1=CC=C(OCCCCC2=CC=CC=C2)C=C1

Pharmacology

Indication

Used as an adjunct to the standard therapy of inhaled steroids with inhaled long- and/or short-acting beta-agonists.

Structured Indications
Not Available
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.

TargetActionsOrganism
ACysteinyl leukotriene receptor 1
antagonist
Human
UTumor necrosis factor
other/unknown
Human
UInterleukin-5
antagonist
Human
UEosinophil cationic protein
other/unknown
Human
UNuclear factor NF-kappa-B p105 subunit
other/unknown
Human
UMucin-2
other/unknown
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AmiodaroneThe serum concentration of Pranlukast can be increased when it is combined with Amiodarone.Approved, Investigational
AtazanavirThe serum concentration of Pranlukast can be increased when it is combined with Atazanavir.Approved, Investigational
BoceprevirThe serum concentration of Pranlukast can be increased when it is combined with Boceprevir.Approved, Withdrawn
CeritinibThe serum concentration of Pranlukast can be increased when it is combined with Ceritinib.Approved
ClarithromycinThe serum concentration of Pranlukast can be increased when it is combined with Clarithromycin.Approved
CobicistatThe serum concentration of Pranlukast can be increased when it is combined with Cobicistat.Approved
DarunavirThe serum concentration of Pranlukast can be increased when it is combined with Darunavir.Approved
IdelalisibThe serum concentration of Pranlukast can be increased when it is combined with Idelalisib.Approved
IndinavirThe serum concentration of Pranlukast can be increased when it is combined with Indinavir.Approved
ItraconazoleThe serum concentration of Pranlukast can be increased when it is combined with Itraconazole.Approved, Investigational
KetoconazoleThe serum concentration of Pranlukast can be increased when it is combined with Ketoconazole.Approved, Investigational
LopinavirThe serum concentration of Pranlukast can be increased when it is combined with Lopinavir.Approved
LoxapineThe risk or severity of adverse effects can be increased when Pranlukast is combined with Loxapine.Approved
NefazodoneThe serum concentration of Pranlukast can be increased when it is combined with Nefazodone.Approved, Withdrawn
NelfinavirThe serum concentration of Pranlukast can be increased when it is combined with Nelfinavir.Approved
PosaconazoleThe serum concentration of Pranlukast can be increased when it is combined with Posaconazole.Approved, Investigational, Vet Approved
SaquinavirThe serum concentration of Pranlukast can be increased when it is combined with Saquinavir.Approved, Investigational
StiripentolThe serum concentration of Pranlukast can be increased when it is combined with Stiripentol.Approved
TelaprevirThe serum concentration of Pranlukast can be increased when it is combined with Telaprevir.Approved, Withdrawn
TelithromycinThe serum concentration of Pranlukast can be increased when it is combined with Telithromycin.Approved
VoriconazoleThe serum concentration of Pranlukast can be increased when it is combined with Voriconazole.Approved, Investigational
Food Interactions
Not 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 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]
External Links
PubChem Compound
4887
PubChem Substance
46508129
ChemSpider
4718
BindingDB
50023198
ChEBI
94810
ChEMBL
CHEMBL21333
Therapeutic Targets Database
DAP000977
PharmGKB
PA134698661
Wikipedia
Pranlukast
ATC Codes
R03DC02 — Pranlukast

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentRhinitis, Allergic, Seasonal1

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
PropertyValueSource
Water Solubility0.0032 mg/mLALOGPS
logP4.82ALOGPS
logP4.67ChemAxon
logS-5.2ALOGPS
pKa (Strongest Acidic)6.86ChemAxon
pKa (Strongest Basic)-1.7ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area119.09 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity139.15 m3·mol-1ChemAxon
Polarizability51.41 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.991
Blood Brain Barrier+0.9446
Caco-2 permeable-0.6689
P-glycoprotein substrateNon-substrate0.5976
P-glycoprotein inhibitor INon-inhibitor0.719
P-glycoprotein inhibitor IINon-inhibitor0.6885
Renal organic cation transporterNon-inhibitor0.8511
CYP450 2C9 substrateNon-substrate0.8643
CYP450 2D6 substrateNon-substrate0.8403
CYP450 3A4 substrateNon-substrate0.5077
CYP450 1A2 substrateNon-inhibitor0.7009
CYP450 2C9 inhibitorNon-inhibitor0.5597
CYP450 2D6 inhibitorNon-inhibitor0.8714
CYP450 2C19 inhibitorNon-inhibitor0.5194
CYP450 3A4 inhibitorNon-inhibitor0.5679
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6646
Ames testAMES toxic0.5986
CarcinogenicityNon-carcinogens0.875
BiodegradationNot ready biodegradable0.997
Rat acute toxicity2.2158 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7439
hERG inhibition (predictor II)Non-inhibitor0.7501
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as chromones. These are compounds containing a benzopyran-4-one moiety.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-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
show 5 more
Substituents
Chromone / Benzamide / Benzoic acid or derivatives / Phenoxy compound / Benzoyl / Phenol ether / Alkyl aryl ether / Pyranone / Monocyclic benzene moiety / Benzenoid
show 18 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Leukotriene receptor activity
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, e...
Gene Name
CYSLTR1
Uniprot ID
Q9Y271
Uniprot Name
Cysteinyl leukotriene receptor 1
Molecular Weight
38540.55 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
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 ac...
Gene Name
TNF
Uniprot ID
P01375
Uniprot Name
Tumor necrosis factor
Molecular Weight
25644.15 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Interleukin-5 receptor binding
Specific Function
Factor that induces terminal differentiation of late-developing B-cells to immunoglobulin secreting cells.
Gene Name
IL5
Uniprot ID
P05113
Uniprot Name
Interleukin-5
Molecular Weight
15237.695 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Ribonuclease activity
Specific Function
Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolariza...
Gene Name
RNASE3
Uniprot ID
P12724
Uniprot Name
Eosinophil cationic protein
Molecular Weight
18385.145 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Transcriptional repressor activity, rna polymerase ii transcription regulatory region sequence-specific binding
Specific Function
NF-kappa-B is a pleiotropic transcription factor present in almost all cell types and is the endpoint of a series of signal transduction events that are initiated by a vast array of stimuli related...
Gene Name
NFKB1
Uniprot ID
P19838
Uniprot Name
Nuclear factor NF-kappa-B p105 subunit
Molecular Weight
105355.175 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Other/unknown
General Function
Not Available
Specific Function
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 s...
Gene Name
MUC2
Uniprot ID
Q02817
Uniprot Name
Mucin-2
Molecular Weight
540296.38 Da
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:15475658]
  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:17223000]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Vitamin d3 25-hydroxylase 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 react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
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]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase 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 un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
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]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Organic anion transmembrane transporter activity
Specific Function
Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter.
Gene Name
ABCC2
Uniprot ID
Q92887
Uniprot Name
Canalicular multispecific organic anion transporter 1
Molecular Weight
174205.64 Da
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]

Drug created on July 17, 2007 06:39 / Updated on December 01, 2017 14:42