Identification

Name
Cinalukast
Accession Number
DB00587  (APRD00637)
Type
Small Molecule
Groups
Approved
Description

Used in the treatment of asthma, cinalukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Cinalukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.

Structure
Thumb
Synonyms
  • 3'-((e)-2-(4-Cyclobutyl-2-thiazolyl)vinyl)-2,2-diethylsuccinanilic acid
  • Cinalukast
External IDs
RO 24-5913 / RO-24-5913
Categories
UNII
5E1O433QAI
CAS number
128312-51-6
Weight
Average: 412.545
Monoisotopic: 412.182063462
Chemical Formula
C23H28N2O3S
InChI Key
BZMKNPGKXJAIDV-VAWYXSNFSA-N
InChI
InChI=1S/C23H28N2O3S/c1-3-23(4-2,22(27)28)14-20(26)24-18-10-5-7-16(13-18)11-12-21-25-19(15-29-21)17-8-6-9-17/h5,7,10-13,15,17H,3-4,6,8-9,14H2,1-2H3,(H,24,26)(H,27,28)/b12-11+
IUPAC Name
3-({3-[(E)-2-(4-cyclobutyl-1,3-thiazol-2-yl)ethenyl]phenyl}carbamoyl)-2,2-diethylpropanoic acid
SMILES
CCC(CC)(CC(=O)NC1=CC=CC(\C=C\C2=NC(=CS2)C2CCC2)=C1)C(O)=O

Pharmacology

Indication

For Protection against second- phase inflamation in exercise-induced bronchoconstriction and Asthma.

Structured Indications
Not Available
Pharmacodynamics

Used in the treatment of asthma, cinalukast selectively antagonizes leukotriene D4 (LTD4) at the cysteinyl leukotriene receptor, CysLT1, in the human airway. Cinalukast inhibits the actions of LTD4 at the CysLT1 receptor, preventing airway edema, smooth muscle contraction, and enhanced secretion of thick, viscous mucus.

Mechanism of action

Binds to the cysteinyl leukotriene receptor. The cysteinyl leukotrienes (LTC4, LTD4, LTE4) are products of arachidonic acid metabolism and are released from various cells, including mast cells and eosinophils. These eicosanoids bind to cysteinyl leukotriene receptors (CysLT) found in the human airway. Cysteinyl leukotrienes and leukotriene receptor occupation have been correlated with the pathophysiology of asthma, including airway edema, smooth muscle contraction, and altered cellular activity associated with the inflammatory process, which contribute to the signs and symptoms of asthma.

TargetActionsOrganism
ACysteinyl leukotriene receptor 1
antagonist
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB14725
PubChem Compound
6436135
PubChem Substance
46505799
ChemSpider
4940804
BindingDB
50064086
ChEBI
126598
ChEMBL
CHEMBL283754
Therapeutic Targets Database
DAP000976
PharmGKB
PA164743057

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.000872 mg/mLALOGPS
logP4.98ALOGPS
logP5.48ChemAxon
logS-5.7ALOGPS
pKa (Strongest Acidic)4.36ChemAxon
pKa (Strongest Basic)2.44ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area79.29 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity116.75 m3·mol-1ChemAxon
Polarizability45.8 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9315
Blood Brain Barrier+0.8337
Caco-2 permeable-0.6145
P-glycoprotein substrateSubstrate0.5433
P-glycoprotein inhibitor INon-inhibitor0.939
P-glycoprotein inhibitor IINon-inhibitor0.9373
Renal organic cation transporterNon-inhibitor0.9402
CYP450 2C9 substrateNon-substrate0.7695
CYP450 2D6 substrateNon-substrate0.8402
CYP450 3A4 substrateNon-substrate0.5901
CYP450 1A2 substrateNon-inhibitor0.7134
CYP450 2C9 inhibitorNon-inhibitor0.6524
CYP450 2D6 inhibitorNon-inhibitor0.9247
CYP450 2C19 inhibitorNon-inhibitor0.6193
CYP450 3A4 inhibitorInhibitor0.7242
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5806
Ames testNon AMES toxic0.7982
CarcinogenicityNon-carcinogens0.857
BiodegradationNot ready biodegradable0.9763
Rat acute toxicity2.5159 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9993
hERG inhibition (predictor II)Non-inhibitor0.9064
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 anilides. These are organic heterocyclic compounds derived from oxoacids RkE(=O)l(OH)m (l not 0) by replacing an OH group by the NHPh group or derivative formed by ring substitution.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Anilides
Direct Parent
Anilides
Alternative Parents
Styrenes / N-arylamides / 2,4-disubstituted thiazoles / Fatty amides / Heteroaromatic compounds / Secondary carboxylic acid amides / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds
show 3 more
Substituents
Anilide / Styrene / N-arylamide / 2,4-disubstituted 1,3-thiazole / Fatty amide / Fatty acyl / Azole / Heteroaromatic compound / Thiazole / Carboxamide group
show 15 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
1,3-thiazole, carboxylic acid (CHEBI:126598)

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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Adelroth E, Inman MD, Summers E, Pace D, Modi M, O'Byrne PM: Prolonged protection against exercise-induced bronchoconstriction by the leukotriene D4-receptor antagonist cinalukast. J Allergy Clin Immunol. 1997 Feb;99(2):210-5. [PubMed:9042047]
  3. Foller M, Mahmud H, Gu S, Wang K, Floride E, Kucherenko Y, Luik S, Laufer S, Lang F: Participation of leukotriene C(4) in the regulation of suicidal erythrocyte death. J Physiol Pharmacol. 2009 Sep;60(3):135-43. [PubMed:19826192]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:40