You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on DrugBank.
Identification
NameAmlexanox
Accession NumberDB01025  (APRD00795)
TypeSmall Molecule
GroupsApproved, Investigational
Description

Amlexanox is an antiallergic drug, clinically effective for atopic diseases, especially allergic asthma and rhinitis. Amlexanox as a topical paste is a well tolerated treatment of recurrent aphthous ulcers. Recurrent aphthous ulcer (RAU) is the most prevalent oral mucosal disease in humans, estimated to affect between 5% and 50% of the general population.

Structure
Thumb
Synonyms
SynonymLanguageCode
2-Amino-7-isopropyl-5-oxo-5H-(1)benzopyrano(2,3-b)pyridine-3-carboxylic acidNot AvailableNot Available
AmlexanoxNot AvailableINN, USAN, JAN
AmlexanoxoSpanishINN
AmlexanoxumLatinINN
AmoxanoxNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
AphthasolNot Available
ElicsNot Available
OraDisc ANot Available
SolfaNot Available
Brand mixturesNot Available
Categories
CAS number68302-57-8
WeightAverage: 298.2934
Monoisotopic: 298.095356946
Chemical FormulaC16H14N2O4
InChI KeySGRYPYWGNKJSDL-UHFFFAOYSA-N
InChI
InChI=1S/C16H14N2O4/c1-7(2)8-3-4-12-9(5-8)13(19)10-6-11(16(20)21)14(17)18-15(10)22-12/h3-7H,1-2H3,(H2,17,18)(H,20,21)
IUPAC Name
2-amino-5-oxo-7-(propan-2-yl)-5H-chromeno[2,3-b]pyridine-3-carboxylic acid
SMILES
CC(C)C1=CC2=C(OC3=NC(N)=C(C=C3C2=O)C(O)=O)C=C1
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassBenzopyrans
SubclassChromenopyridines
Direct parentChromenopyridines
Alternative parentsChromones; Pyranopyridines; Pyridinecarboxylic Acids; Cumenes; Pyranones and Derivatives; Aminopyridines and Derivatives; Primary Aromatic Amines; Enolates; Carboxylic Acids; Polyamines
Substituentschromone; pyranopyridine; cumene; pyridine carboxylic acid; pyridine carboxylic acid or derivative; aminopyridine; pyranone; pyran; benzene; primary aromatic amine; pyridine; carboxylic acid; polyamine; carboxylic acid derivative; enolate; amine; primary amine; organonitrogen compound
Classification descriptionThis compound belongs to the chromenopyridines. These are aromatic heterocyclic compounds structurally characterized by a pyridine ring fused to a chromene moiety.
Pharmacology
IndicationUsed as a paste in the mouth to treat aphthous ulcers (canker sores).
PharmacodynamicsAmlexanox is a mucoadhesive oral paste which has been clinically proven to abort the onset, accelerate healing and resolve the pain of aphthous ulcers (canker sores). It decreases the time ulcers take to heal. Because amlexanox decreases the healing time, it also decreases the pain you feel. Recent studies have also shown that the majority of ulcers can be prevented by application of the paste during the prodromal (pre-ulcerative) phase of the disease. Recurrent Aphthous Ulcers (RAU) also known as Recurrent Aphthous Stomatitis (RAS) is recognized as the most common oral mucosal disease known to man. Estimates suggest that 20% - 25% of the general population suffer at least one incidence of aphthous ulcers each year. Amlexanox is also being investigated for its anti-allergenic and anti-inflammatory properties.
Mechanism of actionAs a benzopyrano-bipyridine carboxylic acid derivative, amlexanox has anti-inflammatory and antiallergic properties. It inhibits chemical mediatory release of the slow-reacting substance of anaphylaxis (SRS-A) and may have antagonistic effects on interleukin-3. When cells are under stress, they release an inactive form of human fibroblast growth factor 1 (FGF-1), a potent mitogen (entity that causes mitosis). Amlexanox binds to FGF1, increasing its conformational stability, sterically blocking Cu(2+) induced oxidation which normally leads to activation of FGF-1.
AbsorptionNo significant absorption directly through the active ulcer. Most of the systemic absorption is via the gastrointestinal tract.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Metabolized to hydroxylated and conjugated metabolites.

Route of eliminationNot Available
Half lifeElimination half-life is 3.5 ± 1.1 hours.
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7639
Blood Brain Barrier - 0.5689
Caco-2 permeable - 0.6574
P-glycoprotein substrate Non-substrate 0.5954
P-glycoprotein inhibitor I Non-inhibitor 0.9502
P-glycoprotein inhibitor II Non-inhibitor 0.9669
Renal organic cation transporter Non-inhibitor 0.9624
CYP450 2C9 substrate Non-substrate 0.82
CYP450 2D6 substrate Non-substrate 0.8797
CYP450 3A4 substrate Non-substrate 0.6051
CYP450 1A2 substrate Non-inhibitor 0.671
CYP450 2C9 substrate Non-inhibitor 0.8017
CYP450 2D6 substrate Non-inhibitor 0.9244
CYP450 2C19 substrate Non-inhibitor 0.7582
CYP450 3A4 substrate Non-inhibitor 0.922
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9501
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.8727
Biodegradation Not ready biodegradable 0.9071
Rat acute toxicity 1.5062 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9942
hERG inhibition (predictor II) Non-inhibitor 0.8609
Pharmacoeconomics
Manufacturers
  • Uluru inc
Packagers
Dosage formsNot Available
Prices
Unit descriptionCostUnit
Aphthasol 5% Paste 3 gm Tube29.99USDtube
Aphthasol 5% paste7.36USDg
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
CountryPatent NumberApprovedExpires (estimated)
United States53627371994-11-082011-11-08
Properties
Statesolid
Experimental Properties
PropertyValueSource
logP4.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.146ALOGPS
logP2.76ALOGPS
logP3.65ChemAxon
logS-3.3ALOGPS
pKa (Strongest Acidic)4.3ChemAxon
pKa (Strongest Basic)0.87ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area102.51 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity81.43 m3·mol-1ChemAxon
Polarizability30.82 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Bell J: Amlexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig. 2005;25(9):555-66. Pubmed
External Links
ResourceLink
KEGG DrugD01828
PubChem Compound2161
PubChem Substance46504508
ChemSpider2076
ChEBI31205
ChEMBLCHEMBL1096
Therapeutic Targets DatabaseDAP000321
PharmGKBPA164745310
Drugs.comhttp://www.drugs.com/cdi/amlexanox.html
ATC CodesA01AD07R03DX01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelshow(129 KB)
MSDSshow(79.7 KB)
Interactions
Drug InteractionsSearched, but no interactions found.
Food InteractionsNot Available

Targets

1. Protein S100-A12

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Protein S100-A12 P80511 Details

References:

  1. Shishibori T, Oyama Y, Matsushita O, Yamashita K, Furuichi H, Okabe A, Maeta H, Hata Y, Kobayashi R: Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. Biochem J. 1999 Mar 15;338 ( Pt 3):583-9. Pubmed
  2. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. Pubmed
  3. Kishimoto K, Kaneko S, Ohmori K, Tamura T, Hasegawa K: Olopatadine suppresses the migration of THP-1 monocytes induced by S100A12 protein. Mediators Inflamm. 2006;2006(1):42726. Pubmed

2. Protein S100-A13

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Protein S100-A13 Q99584 Details

References:

  1. Shishibori T, Oyama Y, Matsushita O, Yamashita K, Furuichi H, Okabe A, Maeta H, Hata Y, Kobayashi R: Three distinct anti-allergic drugs, amlexanox, cromolyn and tranilast, bind to S100A12 and S100A13 of the S100 protein family. Biochem J. 1999 Mar 15;338 ( Pt 3):583-9. Pubmed
  2. Landriscina M, Prudovsky I, Mouta Carreira C, Soldi R, Tarantini F, Maciag T: Amlexanox reversibly inhibits cell migration and proliferation and induces the Src-dependent disassembly of actin stress fibers in vitro. J Biol Chem. 2000 Oct 20;275(42):32753-62. Pubmed
  3. Okada M, Tokumitsu H, Kubota Y, Kobayashi R: Interaction of S100 proteins with the antiallergic drugs, olopatadine, amlexanox, and cromolyn: identification of putative drug binding sites on S100A1 protein. Biochem Biophys Res Commun. 2002 Apr 12;292(4):1023-30. Pubmed
  4. Matsunaga H, Ueda H: Evidence for serum-deprivation-induced co-release of FGF-1 and S100A13 from astrocytes. Neurochem Int. 2006 Aug;49(3):294-303. Epub 2006 Mar 7. Pubmed
  5. Mouta Carreira C, LaVallee TM, Tarantini F, Jackson A, Lathrop JT, Hampton B, Burgess WH, Maciag T: S100A13 is involved in the regulation of fibroblast growth factor-1 and p40 synaptotagmin-1 release in vitro. J Biol Chem. 1998 Aug 28;273(35):22224-31. Pubmed

3. Interleukin-3

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: antagonist

Components

Name UniProt ID Details
Interleukin-3 P08700 Details

References:

  1. Urisu A, Iimi K, Kondo Y, Horiba F, Masuda S, Tsuruta M, Yazaki T, Torii S: [Inhibitory action amlexanox on interleukin-3-induced enhancement of histamine releasability of human leukocytes] Arerugi. 1990 Oct;39(10):1448-54. Pubmed
  2. Nagai H, Suda H, Iwama T, Daikoku M, Yanagihara Y, Koda A: Effect of NZ-107, a newly synthesized pyridazinone derivative, on antigen-induced contraction of human bronchial strips and histamine release from human lung fragments or leukocytes. Int Arch Allergy Immunol. 1992;98(1):57-63. Pubmed

4. Fibroblast growth factor 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Fibroblast growth factor 1 P05230 Details

References:

  1. Rajalingam D, Kumar TK, Soldi R, Graziani I, Prudovsky I, Yu C: Molecular mechanism of inhibition of nonclassical FGF-1 export. Biochemistry. 2005 Nov 29;44(47):15472-9. Pubmed

Comments
comments powered by Disqus
Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:13