DT-Web

DB00716 - Nedocromil


Identification
Name Nedocromil
Accession Number DB00716 (APRD01137)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 371.3408
Groups approved
Monoisotopic Weight 371.100501903
Pharmacology
Indication For the treatment of mild to moderate asthma
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
Protein binding approximately 89% protein bound in human plasma over a concentration range of 0.5 to 50 µg/mL
Biotransformation 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%).
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
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Cysteinyl leukotriene receptor 1
Name Cysteinyl leukotriene receptor 1
Gene Name CYSLTR1
Pharmacological action yes
Actions suppressor
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • 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
  • 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
DTHybrid score 1.0001
Cysteinyl leukotriene receptor 2
Name Cysteinyl leukotriene receptor 2
Gene Name CYSLTR2
Pharmacological action yes
Actions antagonist
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • 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
  • 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
DTHybrid score 1.1596
fMet-Leu-Phe receptor
Name fMet-Leu-Phe receptor
Gene Name FPR1
Pharmacological action unknown
Actions antagonist
References
  • 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
  • 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
  • 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
DTHybrid score 1.1597
Prostaglandin D2 receptor
Name Prostaglandin D2 receptor
Gene Name PTGDR
Pharmacological action unknown
Actions unknown
References
  • Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. - Pubmed
  • 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
  • Lane SJ, Lee TH: Mast cell effector mechanisms. J Allergy Clin Immunol. 1996 Nov;98(5 Pt 2):S67-71; discussion S71-2. - Pubmed
  • 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
DTHybrid score 1.1589
Heat shock protein HSP 90-alpha
Name Heat shock protein HSP 90-alpha
Gene Name HSP90AA1
Pharmacological action unknown
Actions Not Available
References
  • 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
  • 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
DTHybrid score 2.0897

Predictions


Id Partner name Gene Name Score
3456 Heat shock protein HSP 90-beta HSP90AB1 0.1073
2232 Interleukin-5 IL5 0.0375
1593 Mucin-2 MUC2 0.0374
1787 Nuclear factor NF-kappa-B p105 subunit NFKB1 0.0328
4757 Cytochrome P450 2C9 CYP2C9 0.0328
4512 Cytochrome P450 3A4 CYP3A4 0.0308
20 Prostaglandin G/H synthase 1 PTGS1 0.0273
1123 Eosinophil cationic protein RNASE3 0.0272
777 Tumor necrosis factor TNF 0.0251
4924 Cytochrome P450 2C8 CYP2C8 0.0238
275 Arachidonate 5-lipoxygenase ALOX5 0.023
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0185
5718 Cytochrome P450 2A6 CYP2A6 0.0159
1735 Canalicular multispecific organic anion transporter 1 ABCC2 0.0138
4200 Cytochrome P450 1A2 CYP1A2 0.0128
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0122
6013 Cytochrome P450 2E1 CYP2E1 0.0114
6016 Cytochrome P450 2C19 CYP2C19 0.0103
4119 Cytochrome P450 2D6 CYP2D6 0.0095
2091 Endoplasmin HSP90B1 0.0077
512 DNA-directed RNA polymerase alpha chain rpoA 0.0073
5772 DNA-directed RNA polymerase alpha chain rpoA 0.0073
6206 DNA-directed RNA polymerase subunit beta' rpoC 0.0064
284 DNA-directed RNA polymerase beta chain rpoB 0.0059
5773 DNA-directed RNA polymerase beta chain rpoB 0.0059
5315 Chaperone protein htpG htpG 0.0008
5304 UPF0166 protein TM_0021 TM_0021 0.0008
5293 Shikimate kinase 2 aroL 0.0008
5287 Signaling protein Not Available 0.0008
5314 UPF0079 ATP-binding protein HI0065 HI_0065 0.0008
3199 Phosphopantetheine adenylyltransferase coaD 0.0008
3543 Phosphopantetheine adenylyltransferase coaD 0.0008
3567 Phosphopantetheine adenylyltransferase coaD 0.0008
5289 Phosphopantetheine adenylyltransferase coaD 0.0008
5288 Shikimate kinase aroK 0.0008
5276 Chromosomal replication initiator protein dnaA dnaA 0.0008
5292 Putative partitioning protein TT_C1605 0.0008
5266 Activator of hgdC 0.0008
5270 ATP-dependent Clp protease ATP-binding subunit clpX clpX 0.0008
2874 Nitrogenase iron protein 1 nifH1 0.0008
4346 Polynucleotide kinase pseT 0.0008
5281 Plasmid segregation protein parM parM 0.0008
5259 Transcriptional regulator ntrC1 0.0008
6699 Transcriptional regulator Cgl2612 0.0008
4794 Phosphoenolpyruvate carboxykinase [ATP] pckA 0.0008
5305 Phosphoribosylaminoimidazole carboxylase ATPase subunit purK 0.0008
5299 D-alanine--D-alanine ligase ddl 0.0008
6598 D-alanine--D-alanine ligase ddl 0.0008
5275 Multidrug resistance ABC transporter ATP-binding and permease protein lmrA 0.0008
5290 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0008
5638 ATP-dependent hsl protease ATP-binding subunit hslU hslU 0.0008
5284 Large T antigen Not Available 0.0008
5291 Glycogen synthase 1 glgA1 0.0008
3777 ATP-dependent Clp protease ATP-binding subunit clpA clpA 0.0008
5264 DNA replication protein REP 0.0008
5277 Preprotein translocase subunit secA secA 0.0008
5283 D-alanine--D-alanine ligase B ddlB 0.0008
5308 Preprotein translocase secA 1 subunit secA1 0.0008
5285 Kinesin heavy chain KIF5B 0.0008
1549 Heat shock 70 kDa protein 1 HSPA1A 0.0008
3982 Phosphoribosylformylglycinamidine synthase PFAS 0.0008
5261 Phosphoribosylformylglycinamidine synthase purL 0.0008
4106 Guanylate kinase GUK1 0.0007
4516 Guanylate kinase gmk 0.0007
3470 Hypothetical protein MG245 homolog MPN_348 0.0007
5189 Trimethylamine dehydrogenase tmd 0.0007
2284 Adenylate kinase adk 0.0007
2296 Adenylate kinase adk 0.0007
2311 Adenylate kinase adk 0.0007
2312 Adenylate kinase Not Available 0.0007
5302 TrwB trwB 0.0007
4837 Cag-alfa cag-alfa 0.0007
4774 NTPase P4 Not Available 0.0007
5295 2-keto-3-deoxy-gluconate kinase TT_P0036 0.0007
413 Amidophosphoribosyltransferase PPAT 0.0007
2515 Amidophosphoribosyltransferase purF 0.0007
3714 Amidophosphoribosyltransferase purF 0.0007
5646 Galactokinase GALK1 0.0007
3175 Glutamate--cysteine ligase gshA 0.0007
6277 Heat shock cognate 71 kDa protein HSPA8 0.0007
2270 Dephospho-CoA kinase coaE 0.0007
3390 Aminoglycoside 3'-phosphotransferase aphA 0.0007
6029 Aminoglycoside 3'-phosphotransferase aphA1 0.0007
2751 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0007
4755 Holliday junction ATP-dependent DNA helicase ruvB ruvB 0.0007
4838 PMS1 protein homolog 2 PMS2 0.0007
3426 Glutamine synthetase glnA 0.0007
3987 Glutamine synthetase GLUL 0.0007
5265 FtsH ftsH 0.0007
4839 DNA polymerase III subunit tau dnaX 0.0007
2683 Mono-ADP-ribosyltransferase C3 C3 0.0006
2390 Nonsecretory ribonuclease RNASE2 0.0006
5271 Focal adhesion kinase 1 PTK2 0.0006
2922 Glycerol kinase glpK 0.0006
5312 Kinesin-like protein KIF1A KIF1A 0.0006
4366 Riboflavin kinase/FMN adenylyltransferase TM_0857 0.0006
6857 [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 2, mitochondrial PDK2 0.0006
2371 Pantothenate kinase coaA 0.0006
2892 Acetylglutamate kinase argB 0.0006
3550 Acetylglutamate kinase argB 0.0006
2615 Chemotaxis protein cheA cheA 0.0006
3669 Ribokinase rbsK 0.0006
5278 Bifunctional 3'-phosphoadenosine 5'-phosphosulfate synthetase 1 PAPSS1 0.0006
2950 Inositol-trisphosphate 3-kinase A ITPKA 0.0006
825 Arsenical pump-driving ATPase ASNA1 0.0006
3435 Arsenical pump-driving ATPase arsA 0.0006
1881 Hexokinase-1 HK1 0.0006
340 Apoptotic protease-activating factor 1 APAF1 0.0005
5300 Antigen peptide transporter 1 TAP1 0.0005
6390 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 ATP2A1 0.0005
2727 S-adenosylmethionine synthetase metK 0.0005
408 Riboflavin kinase RFK 0.0005
2282 Protein recA recA 0.0005
2315 Protein recA recA 0.0005
2332 Protein recA recA 0.0005
5263 Protein recA recA 0.0005
2334 Dethiobiotin synthetase bioD 0.0005
6555 Dethiobiotin synthetase bioD 0.0005
2697 Uridine-cytidine kinase 2 UCK2 0.0005
2817 Phosphoribosylglycinamide formyltransferase 2 purT 0.0005
6832 Serine/threonine-protein kinase SRPK2 SRPK2 0.0005
137 FolC bifunctional protein [Includes: Folylpolyglutamate synthase folC 0.0005
788 Creatine kinase M-type CKM 0.0005
61 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0005
2644 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0005
2710 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase folK 0.0005
2511 MAP kinase-activated protein kinase 2 MAPKAPK2 0.0005
2317 UDP-N-acetylmuramoylalanine--D-glutamate ligase murD 0.0005
6395 Myosin-14 MYH14 0.0005
453 S-adenosylmethionine synthetase isoform type-1 MAT1A 0.0005
48 Pyridoxal kinase PDXK 0.0005
2251 Thymidylate kinase tmk 0.0005
2254 Thymidylate kinase DTYMK 0.0005
3522 Thymidylate kinase tmk 0.0005
1422 Serine/threonine-protein kinase 6 AURKA 0.0005
702 UMP-CMP kinase CMPK1 0.0005
3379 Kinesin-like protein KIF11 KIF11 0.0005
3822 Actin, alpha skeletal muscle ACTA1 0.0004
2184 Cystic fibrosis transmembrane conductance regulator CFTR 0.0004
201 Glutamate dehydrogenase 1, mitochondrial GLUD1 0.0004
207 Glutathione synthetase GSS 0.0004
5269 Glutathione synthetase gshB 0.0004
504 Mast/stem cell growth factor receptor KIT 0.0004
509 Thymidine kinase TK 0.0004
570 Thymidine kinase TK 0.0004
2559 Thymidine kinase TK 0.0004
3430 Thymidine kinase tdk 0.0004
3518 Thymidine kinase TK 0.0004
5301 Thymidine kinase tdk 0.0004
5771 Thymidine kinase ORF36 0.0004
7009 Thymidine kinase ORF36 0.0004
1721 Glycogen synthase kinase-3 beta GSK3B 0.0004
5294 Nucleoside diphosphate kinase A NME1 0.0004
5682 Ribonuclease pancreatic RNASE1 0.0004
631 3-hydroxy-3-methylglutaryl-coenzyme A reductase HMGCR 0.0004
3387 3-hydroxy-3-methylglutaryl-coenzyme A reductase mvaA 0.0004
4773 Deoxycytidine kinase DCK 0.0003
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