PRANLUKAST

Details

Stereochemistry	ACHIRAL
Molecular Formula	C27H23N5O4
Molecular Weight	481.5026
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

O=C(NC1=CC=CC2=C1OC(=CC2=O)C3=NN=NN3)C4=CC=C(OCCCCC5=CC=CC=C5)C=C4

InChI

InChIKey=NBQKINXMPLXUET-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.drugbank.ca/drugs/DB01411
Curator's Comment: description was created based on several sources, including http://www.e-search.ne.jp/~jpr/PDF/ONO04.PDF

Pranlukast is an antagonist of cysteinyl leukotriene receptor-1 antagonist. It is marketed in Japan by Ono Pharmaceuticals under trademark ONON for the treatment of bronchial asthma and allergic rhinitis as capsules and dry syrup for pediatric use.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Cysteinyl leukotriene receptor 1 20 Target ID: CHEMBL1798 Sources: https://www.ncbi.nlm.nih.gov/pubmed/26985325	Antagonist 2778		23.0 nM [IC50]
Cysteinyl leukotriene receptor 2 3 Target ID: CHEMBL4330 Sources: https://www.ncbi.nlm.nih.gov/pubmed/10851239	Antagonist 2778		3620.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Bronchial asthma 50 Sources: http://www.e-search.ne.jp/~jpr/PDF/ONO04.PDF	Primary	Approved 8429	ONON Approved Use ONON capsules are indicated for treatment of bronchial asthma
Allergic rhinitis 100 Sources: http://www.e-search.ne.jp/~jpr/PDF/ONO04.PDF	Primary	Approved 8429	ONON Approved Use ONON capsules are indicated for treatment of allergic rhinitis
Chronic sinusitis 2 Sources: https://clinicaltrials.gov/ct2/show/NCT00410735	Primary	Phase III 656	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
[Cough-variant asthma successfully treated with a peptide leukotriene receptor antagonist].	1997 Jan	9071168
Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism.	1997 May	9152370
Therapeutic effect of pranlukast, a selective cysteinyl leukotriene receptor antagonist, on bronchial asthma.	1997 Sep	9303339
Development of 2,2-dimethylchromanol cysteinyl LT1 receptor antagonists.	1998 Dec 15	9934474
Pharmacological characterization of the cysteinyl-leukotriene antagonists CGP 45715A (iralukast) and CGP 57698 in human airways in vitro.	1998 Feb	9504401
Effects of the cysteinyl leukotriene receptor antagonists pranlukast and zafirlukast on tracheal mucus secretion in ovalbumin-sensitized guinea-pigs in vitro.	1998 Jun	9647482
Pharmacology of leukotriene receptor antagonists.	1998 Jun	9620942
Leukotriene C4 is a tight-binding inhibitor of microsomal glutathione transferase-1. Effects of leukotriene pathway modifiers.	1999 Jan 22	9890956
Characterization of the human cysteinyl leukotriene CysLT1 receptor.	1999 Jun 24	10391245
Churg-Strauss syndrome after corticosteroid withdrawal in an asthmatic patient treated with pranlukast.	1999 Mar	10069892
Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor.	1999 Sep	10462554
Discovery of CP-199,330 and CP-199,331: two potent and orally efficacious cysteinyl LT1 receptor antagonists devoid of liver toxicity.	1999 Sep 20	10509933
A kinetic binding study to evaluate the pharmacological profile of a specific leukotriene C(4) binding site not coupled to contraction in human lung parenchyma.	2000 Jun	10825389
The protective effects of leukotriene modifiers in aspirin-induced asthma.	2000 Sep 15	19667532
Characterization of the human cysteinyl leukotriene 2 receptor.	2000 Sep 29	10851239
Effects of pranlukast, a cysteinyl leukotriene receptor 1 antagonist, combined with inhaled beclomethasone in patients with moderate or severe asthma.	2001 Aug	11527250
Effects of pranlukast, a leukotriene receptor antagonist, on airway inflammation in mild asthmatics.	2001 Feb	11256554
Churg-Strauss syndrome after reduction of inhaled corticosteroid in a patient treated with pranlukast for asthma.	2001 May	11393418
Molecular cloning and functional characterization of murine cysteinyl-leukotriene 1 (CysLT(1)) receptors.	2001 Nov 1	11705452
Fulminant eosinophilic endomyocarditis in an asthmatic patient treated with pranlukast after corticosteroid withdrawal.	2001 Sep	11514498
Evaluation of the combined effect of pranlukast during high-dose steroid inhalation.	2002	12489251
Pharmacological differences among CysLT(1) receptor antagonists with respect to LTC(4) and LTD(4) in human lung parenchyma.	2002 Apr 15	11996896
Leukotriene C4 synthase gene A(-444)C polymorphism and clinical response to a CYS-LT(1) antagonist, pranlukast, in Japanese patients with moderate asthma.	2002 Oct	12360108
Long-term observations of the clinical course after step down of corticosteroid inhalation therapy in adult chronic asthmatics: correlation with serum levels of eosinophil cationic protein.	2002 Sep	12153692
Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma.	2003	14650364
[Clinical effects of long-term administration of pranlukast, a leukotriene receptor antagonist, on adult patients with bronchial asthma].	2003 Oct	14584388
Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes.	2004 May	15370959
Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.	2005 Feb	15650315
Evaluation of theophylline or pranlukast, a cysteinyl leukotriene receptor 1 antagonist, as add-on therapy in uncontrolled asthmatic patients with a medium dose of inhaled corticosteroids.	2005 Jul-Aug	16270722
Cysteinyl leukotriene receptor 1 is involved in N-methyl-D-aspartate-mediated neuronal injury in mice.	2006 Dec	17112405
Role of regular treatment with inhaled corticosteroid or leukotriene receptor antagonist in mild intermittent asthma.	2008 Mar-Apr	18430318
Antileukotriene drugs in the treatment of asthma.	2010 Mar	20332717
Over-expression of the LTC4 synthase gene in mice reproduces human aspirin-induced asthma.	2011 Aug	21429049
A multifactorial approach to hepatobiliary transporter assessment enables improved therapeutic compound development.	2013 Nov	23956101

Patents

Sample Use Guides

In Vivo Use Guide

The usual adult dosage for oral use is 450 mg of pranlukast hydrate (4 capsules) daily in two divided doses after each meal in the morning and evening. The dosage may be adjusted according to the patient's age and symptoms.

Route of Administration: Oral

In Vitro Use Guide

The activity of pranlukast was measured using calcium mobilization assay. HEK 293 cells stably expressing CysLT1 receptor and Gα16 protein were loaded with 2 uM Fluo-4 AM in Hanks balanced salt solution buffer. The compound was added to a solution, and after 10 min incubation at room temperature, 25 uL LTD4 was dispensed into the well using a FlexStation II microplate reader, and intracellular calcium change was recorded with an excitation wavelength of 485 nm and an emission wavelength of 525 nm. The IC50 for pranlukast was 23 nM.

Name

Type

Language

PRANLUKAST

Official Name

English

PRANLUKAST [MART.]

Common Name

English

ONO-1078

Code

English

RS-411

Code

English

SB-205312

Code

English

pranlukast [INN]

Common Name

English

RS 411

Code

English

Pranlukast [WHO-DD]

Common Name

English

BENZAMIDE, N-(4-OXO-2-(2H-TETRAZOL-5-YL)-4H-1-BENZOPYRAN-8-YL)-4-(4-PHENYLBUTOXY)-

Systematic Name

English

SB 205312

Code

English

PRANLUKAST [MI]

Common Name

English

ONO 1078

Code

English

AZLAIRE

Brand Name

English

CCN-00401

Code

English

ONON

Brand Name

English

CCN 00401

Code

English

N-(4-OXO-2-(1H-TETRAZOL-5-YL)-4H-1-BENZOPYRAN-8-YL)-P-(4-PHENYLBUTOXY)BENZAMIDE

Common Name

English

Classification Tree Code System Code

WHO-VATC

QR03DC02