Banner
targets (5)
for drugs
Identification
Name Nedocromil
Accession Number DB00716 (APRD01137)
Type small molecule
Groups approved
Description

A pyranoquinolone derivative that inhibits activation of inflammatory cells which are associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Alocril
Nedocromil [USAN:BAN:INN]
Nedocromilo [Spanish]
Nedocromilum [Latin]
Tilade
Brand mixtures Not Available
Categories
  • Anti-Asthmatic Agents
  • Anti-inflammatory Agents
  • Anti-Allergic Agents
CAS number 69049-73-6
Weight Average: 371.3408
Monoisotopic: 371.100501903
Chemical Formula C19H17NO7
InChI Key InChIKey=RQTOOFIXOKYGAN-UHFFFAOYSA-N
InChI
InChI=1S/C19H17NO7/c1-3-5-9-16-10(13(21)7-12(18(23)24)20(16)4-2)6-11-14(22)8-15(19(25)26)27-17(9)11/h6-8H,3-5H2,1-2H3,(H,23,24)(H,25,26)
Plain Text
IUPAC Name
9-ethyl-4,6-dioxo-10-propyl-4H,6H,9H-chromeno[7,6-b]pyridine-2,8-dicarboxylic acid
SMILES
CCCC1=C2N(CC)C(=CC(=O)C2=CC2=C1OC(=CC2=O)C(O)=O)C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Chromones
  • (Iso)quinolines and Derivatives
  • Fluoroquinolones and Quinolones
Substructures
  • Hydroxy Compounds
  • Acetates
  • Pyridines and Derivatives
  • Benzene and Derivatives
  • Chromones
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Aromatic compounds
  • (Iso)quinolines and Derivatives
  • Imines
  • Fluoroquinolones and Quinolones
Pharmacology
Indication For the treatment of mild to moderate asthma
Pharmacodynamics Nedocromil is a anti-inflammatory agent and can be administered directly to the bronchial mucosa. It has significant inhibitory effect on allergen-induced early and late asthmatic reactions and on bronchial hyperresponsiveness.
Mechanism of action Nedocromil has been shown to inhibit the in vitro activation of, and mediator release from, a variety of inflammatory cell types associated with asthma, including eosinophils, neutrophils, macrophages, mast cells, monocytes, and platelets. Nedocromil inhibits activation and release of inflammatory mediators such as histamine, prostaglandin D2 and leukotrienes c4 from different types of cells in the lumen and mucosa of the bronchial tree. These mediators are derived from arachidonic acid metabolism through the lipoxygenase and cyclo-oxygenase pathways. The mechanism of action of nedocromil may be due partly to inhibition of axon reflexes and release of sensory neuropeptides, such as substance P, neurokinin A, and calcitonin-geneñrelated peptides. The result is inhibition of bradykinin-induced bronchoconstriction. Nedocromil does not posess any bronchodilator, antihistamine, or corticosteroid activity.
Absorption Low
Volume of distribution Not Available
Protein binding approximately 89% protein bound in human plasma over a concentration range of 0.5 to 50 µg/mL
Metabolism Nedocromil is not metabolized after IV administration and is excreted unchanged.
Route of elimination It is not metabolized and is eliminated primarily unchanged in urine (70%) and feces (30%).
Half life ~3.3 hours
Clearance Not Available
Toxicity Side effects include headache, nasal congestion, ocular burning, irritation and stinging, unpleasant taste, cough, difficulty breathing, noisy breathing, shortness of breath, tightness in chest, wheezing, conjunctivitis, blurred vision, change in color vision, difficulty seeing at night, increased sensitivity of eyes to sunlight.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • King pharmaceuticals inc
  • Allergan inc
  • Sanofi aventis us llc
Packagers
Dosage forms
Form Route Strength
Liquid Ophthalmic
Prices
Unit description Cost Unit
Alocril 2% Solution 5ml Bottle 100.57 USD bottle
Alocril 2% eye drops 19.34 USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Country Patent Number Approved Expires (estimated)
United States RE38628 1992-08-22 2012-08-22
Properties
State solid
Experimental Properties
Property Value Source
melting point 299 dec °C PhysProp
water solubility 145 mg/L Not Available
logP 2.22 SANGSTER (1994)
Predicted Properties
Property Value Source
water solubility 4.59e-02 g/l ALOGPS
logP 2.18 ALOGPS
logP 2.5 ChemAxon
logS -3.9 ALOGPS
pKa (strongest acidic) 2.28 ChemAxon
pKa (strongest basic) -4.2 ChemAxon
physiological charge -2 ChemAxon
hydrogen acceptor count 8 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 121.21 ChemAxon
rotatable bond count 5 ChemAxon
refractivity 98.09 ChemAxon
polarizability 36.95 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D05129 Link_out
KEGG Compound C07255 Link_out
PubChem Compound 50294 Link_out
PubChem Substance 46507587 Link_out
ChemSpider 45608 Link_out
ChEBI 7492 Link_out
ChEMBL 7492 Link_out
PharmGKB PA450601 Link_out
Drug Product Database 2241407 Link_out
RxList http://www.rxlist.com/cgi/generic3/nedocr.htm Link_out
Drugs.com http://www.drugs.com/cdi/nedocromil-drops.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/til1444.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/Nedocromil Link_out
ATC Codes
  • R01AC07
  • R03BC03
  • S01GX04
AHFS Codes
  • 92:00.00
PDB Entries Not Available
FDA label show (362 KB)
MSDS Not Available
Interactions
Drug Interactions Searched, but no interactions found.
Food Interactions Not Available
Targets

1. Cysteinyl leukotriene receptor 1

Pharmacological action: yes
Actions: suppressor

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

Organism class: human
UniProt ID: Q9Y271 Link_out
Gene: CYSLTR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Monteseirin J, Chacon P, Vega A, Sanchez-Monteseirin H, Asturias JA, Martinez A, Guardia P, Perez-Cano R, Conde J: L-selectin expression on neutrophils from allergic patients. Clin Exp Allergy. 2005 Sep;35(9):1204-13. Pubmed
  4. Yazid S, Leoni G, Getting SJ, Cooper D, Solito E, Perretti M, Flower RJ: Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1718-24. Epub 2010 Jun 17. Pubmed
  5. Radeau T, Godard P, Chavis C, Michel FB, Descomps B, Damon M: Effect of nedocromil sodium on sulfidopeptide leukotrienes-stimulated human alveolar macrophages in asthma. Pulm Pharmacol. 1993 Mar;6(1):27-31. Pubmed

2. Cysteinyl leukotriene receptor 2

Pharmacological action: yes
Actions: antagonist

Receptor for cysteinyl leukotrienes. The response is mediated via a G-protein that activates a phosphatidylinositol- calcium second messenger system. Stimulation by BAY u9773, a partial agonist, induces specific contractions of pulmonary veins and might also have an indirect role in the relaxation of the pulmonary vascular endothelium. The rank order of affinities for the leukotrienes is LTC4 = LTD4 >> LTE4

Organism class: human
UniProt ID: Q9NS75 Link_out
Gene: CYSLTR2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Monteseirin J, Chacon P, Vega A, Sanchez-Monteseirin H, Asturias JA, Martinez A, Guardia P, Perez-Cano R, Conde J: L-selectin expression on neutrophils from allergic patients. Clin Exp Allergy. 2005 Sep;35(9):1204-13. Pubmed
  4. Yazid S, Leoni G, Getting SJ, Cooper D, Solito E, Perretti M, Flower RJ: Antiallergic cromones inhibit neutrophil recruitment onto vascular endothelium via annexin-A1 mobilization. Arterioscler Thromb Vasc Biol. 2010 Sep;30(9):1718-24. Epub 2010 Jun 17. Pubmed

3. fMet-Leu-Phe receptor

Pharmacological action: unknown
Actions: antagonist

High affinity receptor for N-formyl-methionyl peptides, which are powerful neutrophils chemotactic factors. Binding of FMLP to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P21462 Link_out
Gene: FPR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Peroni DG, Melotti P, Piacentini GL, Bonizzato C, Boner AL: Effects of nedocromil sodium on the binding of N-formyl-methionyl-leucyl-phenylalanine in human neutrophils. Agents Actions. 1992 Jul;36(3-4):212-4. Pubmed
  2. Carolan EJ, Casale TB: Effects of nedocromil sodium and WEB 2086 on chemoattractant-stimulated neutrophil migration through cellular and noncellular barriers. Ann Allergy. 1992 Oct;69(4):323-8. Pubmed
  3. Warringa RA, Mengelers HJ, Maikoe T, Bruijnzeel PL, Koenderman L: Inhibition of cytokine-primed eosinophil chemotaxis by nedocromil sodium. J Allergy Clin Immunol. 1993 Mar;91(3):802-9. Pubmed

4. Prostaglandin D2 receptor

Pharmacological action: unknown
Actions: unknown

Receptor for prostaglandin D2 (PGD2). The activity of this receptor is mainly mediated by G(s) proteins that stimulate adenylate cyclase, resulting in an elevation of intracellular cAMP. A mobilization of calcium is also observed, but without formation of inositol 1,4,5-trisphosphate

Organism class: human
UniProt ID: Q13258 Link_out
Gene: PTGDR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
  3. Lane SJ, Lee TH: Mast cell effector mechanisms. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2. Pubmed
  4. Ahluwalia P, Anderson DF, Wilson SJ, McGill JI, Church MK: Nedocromil sodium and levocabastine reduce the symptoms of conjunctival allergen challenge by different mechanisms. J Allergy Clin Immunol. 2001 Sep;108(3):449-54. Pubmed

5. Heat shock protein HSP 90-alpha

Pharmacological action: unknown

Molecular chaperone. Has ATPase activity

Organism class: human
UniProt ID: P07900 Link_out
Gene: HSP90AA1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Okada M, Itoh H, Hatakeyama T, Tokumitsu H, Kobayashi R: Hsp90 is a direct target of the anti-allergic drugs disodium cromoglycate and amlexanox. Biochem J. 2003 Sep 1;374(Pt 2):433-41. Pubmed
  2. Nishikawa M, Takemoto S, Takakura Y: Heat shock protein derivatives for delivery of antigens to antigen presenting cells. Int J Pharm. 2008 Apr 16;354(1-2):23-7. Epub 2007 Sep 29. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19