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Identification
- Summary
Pranlukast is a leukotriene receptor antagonist for the treatment of allergic rhinitis and asthma symptoms.
- Generic Name
- Pranlukast
- DrugBank Accession Number
- DB01411
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Pranlukast (DB01411)
- Weight
- Average: 481.512
Monoisotopic: 481.175004241 - Chemical Formula
- C27H23N5O4
- Synonyms
- Pranlukast
- External IDs
- CCN 00401
- CCN-00401
- ONO 1078
- ONO-1078
- ONO-RS 411
- RS 411
- RS-411
- SB 205312
- SB-205312
Pharmacology
- Indication
Used as an adjunct to the standard therapy of inhaled steroids with inhaled long- and/or short-acting beta-agonists.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Allergic rhinitis (ar) •••••••••••• ••••••• ••• ••••••••• •••••• Treatment of Allergic rhinitis (ar) •••••••••••• Treatment of Asthma •••••••••••• ••••••• ••• ••••••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- 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.
Target Actions Organism ACysteinyl leukotriene receptor 1 antagonistHumans UTumor necrosis factor other/unknownHumans UInterleukin-5 antagonistHumans UEosinophil cationic protein other/unknownHumans UNuclear factor NF-kappa-B p105 subunit other/unknownHumans UMucin-2 other/unknownHumans UNuclear factor NF-kappa-B inhibitorHumans - 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
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Side effects include headache, abdominal or stomach pain, cough, dental pain, dizziness, fever, heartburn, skin rash, stuffy nose, weakness or unusual tiredness.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your softwareAbametapir The serum concentration of Pranlukast can be increased when it is combined with Abametapir. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Pranlukast. Acenocoumarol The metabolism of Acenocoumarol can be decreased when combined with Pranlukast. Acetohexamide The metabolism of Acetohexamide can be decreased when combined with Pranlukast. Acetylsalicylic acid The metabolism of Acetylsalicylic acid can be decreased when combined with Pranlukast. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Pranlukast hydrate FR702N558K 150821-03-7 MSXTUBJFNBZPGC-UHFFFAOYSA-N
Categories
- ATC Codes
- R03DC02 — Pranlukast
- Drug Categories
- Agents to Treat Airway Disease
- Anti-Asthmatic Agents
- Benzopyrans
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates (strength unknown)
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Drugs for Obstructive Airway Diseases
- Heterocyclic Compounds, Fused-Ring
- Hormone Antagonists
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Leukotriene Antagonists
- Pyrans
- Respiratory System Agents
- Chemical TaxonomyProvided by Classyfire
- 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
- Alkyl aryl ether / Aromatic heteropolycyclic compound / Azacycle / Azole / Benzamide / Benzenoid / Benzoic acid or derivatives / Benzoyl / Carboxamide group / Carboxylic acid derivative show 18 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- TB8Z891092
- CAS number
- 103177-37-3
- 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
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
- External Links
- PubChem Compound
- 4887
- PubChem Substance
- 46508129
- ChemSpider
- 4718
- BindingDB
- 50023198
- ChEBI
- 94810
- ChEMBL
- CHEMBL21333
- ZINC
- ZINC000001542146
- Therapeutic Targets Database
- DAP000977
- PharmGKB
- PA134698661
- PDBe Ligand
- KNT
- Wikipedia
- Pranlukast
- PDB Entries
- 6rz4
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Chronic Sinusitis 1 somestatus stop reason just information to hide 3 Completed Treatment Seasonal Allergic Rhinitis 1 somestatus stop reason just information to hide 1 Unknown Status Treatment Healthy Volunteers (HV) 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Powder Oral Capsule Oral - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0032 mg/mL ALOGPS logP 4.82 ALOGPS logP 4.67 Chemaxon logS -5.2 ALOGPS pKa (Strongest Acidic) 6.86 Chemaxon pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 7 Chemaxon Hydrogen Donor Count 2 Chemaxon Polar Surface Area 119.09 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 139.15 m3·mol-1 Chemaxon Polarizability 51.41 Å3 Chemaxon Number of Rings 5 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - 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 inhibitor Non-inhibitor 0.5597 CYP450 2D6 inhibitor Non-inhibitor 0.8714 CYP450 2C19 inhibitor Non-inhibitor 0.5194 CYP450 3A4 inhibitor 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
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-1340900000-56f64f3c9e341a9e0dee Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-001r-0005900000-b18c3becb89797a689c9 Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-001i-1511900000-3ba61725c3b435b5629d Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-00l7-9314500000-03d16a78e7ba240a76ce Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-000x-9610700000-5606846bc3cbed27bfc6 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0019-4435900000-51aed43770663045dd4e Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 235.9053621 predictedDarkChem Lite v0.1.0 [M-H]- 200.57753 predictedDeepCCS 1.0 (2019) [M+H]+ 238.9091621 predictedDarkChem Lite v0.1.0 [M+H]+ 202.9731 predictedDeepCCS 1.0 (2019) [M+Na]+ 237.3226621 predictedDarkChem Lite v0.1.0 [M+Na]+ 208.88562 predictedDeepCCS 1.0 (2019)
Targets
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Use our structured and evidence-based datasets to unlock newinsights and accelerate drug research.
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General 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
- Specific Function
- Cysteinyl leukotriene receptor activity
- Gene Name
- CYSLTR1
- Uniprot ID
- Q9Y271
- Uniprot Name
- Cysteinyl leukotriene receptor 1
- Molecular Weight
- 38540.55 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Singh RK, Tandon R, Dastidar SG, Ray A: A review on leukotrienes and their receptors with reference to asthma. J Asthma. 2013 Nov;50(9):922-31. doi: 10.3109/02770903.2013.823447. Epub 2013 Aug 16. [Article]
- Suzuki S, Takeuchi K, Ishinaga H, Basbaum C, Majima Y: Leukotriene D4 upregulates MUC2 gene transcription in human epithelial cells. Pharmacology. 2008;81(3):221-8. doi: 10.1159/000112866. Epub 2008 Jan 7. [Article]
- Haneda Y, Hasegawa S, Hirano R, Hashimoto K, Ohsaki A, Ichiyama T: Leukotriene D4 enhances tumor necrosis factor-alpha-induced vascular endothelial growth factor production in human monocytes/macrophages. Cytokine. 2011 Jul;55(1):24-8. doi: 10.1016/j.cyto.2011.03.018. Epub 2011 Apr 8. [Article]
- 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. [Article]
- Saito K, Nagata M, Kikuchi I, Sakamoto Y: Leukotriene D4 and eosinophil transendothelial migration, superoxide generation, and degranulation via beta2 integrin. Ann Allergy Asthma Immunol. 2004 Dec;93(6):594-600. doi: 10.1016/S1081-1206(10)61269-0. [Article]
- Figueroa EE, Kramer M, Strange K, Denton JS: CysLT1 receptor antagonists pranlukast and zafirlukast inhibit LRRC8-mediated volume regulated anion channels independently of the receptor. Am J Physiol Cell Physiol. 2019 Oct 1;317(4):C857-C866. doi: 10.1152/ajpcell.00281.2019. Epub 2019 Aug 7. [Article]
- Reques FG, Rodriguez JL: Tolerability of leukotriene modifiers in asthma: a review of clinical experience. BioDrugs. 1999 Jun;11(6):385-94. doi: 10.2165/00063030-199911060-00003. [Article]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other/unknown
- General 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. Impairs regulatory T-cells (Treg) function in individuals with rheumatoid arthritis via FOXP3 dephosphorylation. Up-regulates the expression of protein phosphatase 1 (PP1), which dephosphorylates the key 'Ser-418' residue of FOXP3, thereby inactivating FOXP3 and rendering Treg cells functionally defective (PubMed:23396208). Key mediator of cell death in the anticancer action of BCG-stimulated neutrophils in combination with DIABLO/SMAC mimetic in the RT4v6 bladder cancer cell line (PubMed:16829952, PubMed:22517918, PubMed:23396208). Induces insulin resistance in adipocytes via inhibition of insulin-induced IRS1 tyrosine phosphorylation and insulin-induced glucose uptake. Induces GKAP42 protein degradation in adipocytes which is partially responsible for TNF-induced insulin resistance (By similarity). Plays a role in angiogenesis by inducing VEGF production synergistically with IL1B and IL6 (PubMed:12794819). Promotes osteoclastogenesis and therefore mediates bone resorption (By similarity)
- Specific Function
- Cytokine activity
- Gene Name
- TNF
- Uniprot ID
- P01375
- Uniprot Name
- Tumor necrosis factor
- Molecular Weight
- 25644.15 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Antagonist
- General Function
- Homodimeric cytokine expressed predominantly by T-lymphocytes and NK cells that plays an important role in the survival, differentiation, and chemotaxis of eosinophils (PubMed:2653458, PubMed:9010276). Acts also on activated and resting B-cells to induce immunoglobulin production, growth, and differentiation (By similarity). Mechanistically, exerts its biological effects through a receptor composed of IL5RA subunit and the cytokine receptor common subunit beta/CSF2RB (PubMed:1495999, PubMed:22528658). Binding to the receptor leads to activation of various kinases including LYN, SYK and JAK2 and thereby propagates signals through the RAS-MAPK and JAK-STAT5 pathways respectively (PubMed:7613138)
- Specific Function
- Cytokine activity
- Gene Name
- IL5
- Uniprot ID
- P05113
- Uniprot Name
- Interleukin-5
- Molecular Weight
- 15237.695 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other/unknown
- General Function
- Cytotoxin and helminthotoxin with low-efficiency ribonuclease activity. Possesses a wide variety of biological activities. Exhibits antibacterial activity, including cytoplasmic membrane depolarization of preferentially Gram-negative, but also Gram-positive strains. Promotes E.coli outer membrane detachment, alteration of the overall cell shape and partial loss of cell content
- Specific Function
- Endonuclease activity
- Gene Name
- RNASE3
- Uniprot ID
- P12724
- Uniprot Name
- Eosinophil cationic protein
- Molecular Weight
- 18385.145 Da
References
- 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. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other/unknown
- General 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 to many biological processes 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
- Specific Function
- Actinin binding
- Gene Name
- NFKB1
- Uniprot ID
- P19838
- Uniprot Name
- Nuclear factor NF-kappa-B p105 subunit
- Molecular Weight
- 105355.175 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Other/unknown
- General Function
- Coats the epithelia of the intestines and other mucus membrane-containing organs to provide a protective, lubricating barrier against particles and infectious agents at mucosal surfaces (PubMed:17058067, PubMed:19432394, PubMed:33031746). Major constituent of the colon mucus, which is mainly formed by large polymeric networks of MUC2 secreted by goblet cells that cover the exposed surfaces of intestine (PubMed:19432394, PubMed:33031746). MUC2 networks form hydrogels that guard the underlying epithelium from pathogens and other hazardous matter entering from the outside world, while permitting nutrient absorption and gas exchange (PubMed:33031746, PubMed:36206754). Acts as a divalent copper chaperone that protects intestinal cells from copper toxicity and facilitates nutritional copper unptake into cells (PubMed:36206754). Binds both Cu(2+) and its reduced form, Cu(1+), at two juxtaposed binding sites: Cu(2+), once reduced to Cu(1+) by vitamin C (ascorbate) or other dietary antioxidants, transits to the other binding site (PubMed:36206754). MUC2-bound Cu(1+) is protected from oxidation in aerobic environments, and can be released for nutritional delivery to cells (PubMed:36206754). Mucin gels store antimicrobial molecules that participate in innate immunity (PubMed:33031746). Mucin glycoproteins also house and feed the microbiome, lubricate tissue surfaces, and may facilitate the removal of contaminants and waste products from the body (PubMed:33031746). Goblet cells synthesize two forms of MUC2 mucin that differ in branched chain O-glycosylation and the site of production in the colon: a (1) 'thick' mucus that wraps the microbiota to form fecal pellets is produced in the proximal, ascending colon (By similarity). 'Thick' mucus transits along the descending colon and is lubricated by a (2) 'thin' MUC2 mucus produced in the distal colon which adheres to the 'thick' mucus (By similarity)
- Specific Function
- Cupric ion binding
- Gene Name
- MUC2
- Uniprot ID
- Q02817
- Uniprot Name
- Mucin-2
- Molecular Weight
- 550846.44 Da
References
- 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. [Article]
- 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. [Article]
- Kind
- Protein group
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General 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 to many biological processes 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. 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. In a non-canonical activation pathway, the MAP3K14-activated CHUK/IKKA homodimer phosphorylates NFKB2/p100 associated with RelB, inducing its proteolytic processing to NFKB2/p52 and the formation of NF-kappa-B RelB-p52 complexes. The NF-kappa-B heterodimeric RelB-p52 complex is a transcriptional activator. The NF-kappa-B p52-p52 homodimer is a transcriptional repressor. NFKB2 appears to have dual functions such as cytoplasmic retention of attached NF-kappa-B proteins by p100 and generation of p52 by a cotranslational processing. The proteasome-mediated process ensures the production of both p52 and p100 and preserves their independent function. p52 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. p52 and p100 are respectively the minor and major form; the processing of p100 being relatively poor. Isoform p49 is a subunit of the NF-kappa-B protein complex, which stimulates the HIV enhancer in synergy with p65. In concert with RELB, regulates the circadian clock by repressing the transcriptional activator activity of the CLOCK-BMAL1 heterodimer
- Specific Function
- Dna-binding transcription activator activity, rna polymerase ii-specific
Components:
| Name | UniProt ID |
|---|---|
| Nuclear factor NF-kappa-B p100 subunit | Q00653 |
| Nuclear factor NF-kappa-B p105 subunit | P19838 |
References
- 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. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Inhibitor
- Curator comments
- Data supporting this enzyme action are limited to the findings of 1 in vitro study.
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
- Specific Function
- (r)-limonene 6-monooxygenase activity
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Liu KH, Lee YM, Shon JH, Kim MJ, Lee SS, Yoon YR, Cha IJ, Shin JG: Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes. Xenobiotica. 2004 May;34(5):429-38. doi: 10.1080/00498250410001691253 . [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
- Specific Function
- 1,8-cineole 2-exo-monooxygenase activity
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- 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. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates (PubMed:10220572, PubMed:10421658, PubMed:11500505, PubMed:16332456). Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification (PubMed:10421658). Mediates also hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 (PubMed:11500505). Transports sulfated bile salt such as taurolithocholate sulfate (PubMed:16332456). Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors (PubMed:10220572, PubMed:11500505, PubMed:12441801). Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine (PubMed:10220572, PubMed:11500505)
- Specific Function
- Abc-type glutathione s-conjugate transporter activity
- Gene Name
- ABCC2
- Uniprot ID
- Q92887
- Uniprot Name
- ATP-binding cassette sub-family C member 2
- Molecular Weight
- 174205.64 Da
References
- 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. [Article]
Drug created at July 17, 2007 12:39 / Updated at June 12, 2021 10:52