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Identification
NameAmlexanox
Accession NumberDB01025  (APRD00795)
TypeSmall Molecule
GroupsApproved, Investigational
DescriptionAmlexanox 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
2-Amino-7-isopropyl-5-oxo-5H-(1)benzopyrano(2,3-b)pyridine-3-carboxylic acid
Amlexanox
Amlexanoxo
Amlexanoxum
Amoxanox
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Aptherapaste5 %oralPharmascience IncNot applicableNot applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AphthasolNot Available
ElicsNot Available
OraDisc ANot Available
SolfaNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNIIBRL1C2459K
CAS number68302-57-8
WeightAverage: 298.2934
Monoisotopic: 298.095356946
Chemical FormulaC16H14N2O4
InChI KeyInChIKey=SGRYPYWGNKJSDL-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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as chromenopyridines. These are aromatic heterocyclic compounds structurally characterized by a pyridine ring fused to a chromene moiety.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzopyrans
Sub Class1-benzopyrans
Direct ParentChromenopyridines
Alternative Parents
Substituents
  • Chromenopyridine
  • Chromone
  • Pyranopyridine
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Cumene
  • Pyranone
  • Aminopyridine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • Pyran
  • Primary aromatic amine
  • Heteroaromatic compound
  • Vinylogous amide
  • Oxacycle
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+0.7639
Blood Brain Barrier-0.5689
Caco-2 permeable-0.6574
P-glycoprotein substrateNon-substrate0.5954
P-glycoprotein inhibitor INon-inhibitor0.9502
P-glycoprotein inhibitor IINon-inhibitor0.9669
Renal organic cation transporterNon-inhibitor0.9624
CYP450 2C9 substrateNon-substrate0.82
CYP450 2D6 substrateNon-substrate0.8797
CYP450 3A4 substrateNon-substrate0.6051
CYP450 1A2 substrateNon-inhibitor0.671
CYP450 2C9 inhibitorNon-inhibitor0.8017
CYP450 2D6 inhibitorNon-inhibitor0.9244
CYP450 2C19 inhibitorNon-inhibitor0.7582
CYP450 3A4 inhibitorNon-inhibitor0.922
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9501
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.8727
BiodegradationNot ready biodegradable0.9071
Rat acute toxicity1.5062 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9942
hERG inhibition (predictor II)Non-inhibitor0.8609
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Pasteoral5 %
Prices
Unit descriptionCostUnit
Aphthasol 5% Paste 3 gm Tube29.99USD tube
Aphthasol 5% paste7.36USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5362737 No1994-11-082011-11-08Us
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP4.1Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.146 mg/mLALOGPS
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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General References
  1. Bell J: Amlexanox for the treatment of recurrent aphthous ulcers. Clin Drug Investig. 2005;25(9):555-66. [PubMed:17532700 ]
External Links
ATC CodesA01AD07R03DX01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelDownload (129 KB)
MSDSDownload (79.7 KB)
Interactions
Drug InteractionsNo interactions found.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
S100A12 is a calcium-, zinc- and copper-binding protein which plays a prominent role in the regulation of inflammatory processes and immune response. Its proinflammatory activity involves recruitment of leukocytes, promotion of cytokine and chemokine production, and regulation of leukocyte adhesion and migration. Acts as an alarmin or a danger associated molecular pattern (DAMP) molecule and st...
Gene Name:
S100A12
Uniprot ID:
P80511
Molecular Weight:
10574.975 Da
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:10051426 ]
  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:11944917 ]
  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:16864903 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Zinc ion binding
Specific Function:
Plays a role in the export of proteins that lack a signal peptide and are secreted by an alternative pathway. Binds two calcium ions per subunit. Binds one copper ion. Binding of one copper ion does not interfere with calcium binding. Required for the copper-dependent stress-induced export of IL1A and FGF1. The calcium-free protein binds to lipid vesicles containing phosphatidylserine, but not ...
Gene Name:
S100A13
Uniprot ID:
Q99584
Molecular Weight:
11471.095 Da
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:10051426 ]
  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:10921913 ]
  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:11944917 ]
  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:16519964 ]
  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:9712836 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
Interleukin-3 receptor binding
Specific Function:
Granulocyte/macrophage colony-stimulating factors are cytokines that act in hematopoiesis by controlling the production, differentiation, and function of 2 related white cell populations of the blood, the granulocytes and the monocytes-macrophages.This CSF induces granulocytes, macrophages, mast cells, stem cells, erythroid cells, eosinophils and megakaryocytes.
Gene Name:
IL3
Uniprot ID:
P08700
Molecular Weight:
17232.905 Da
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:1701989 ]
  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:1378042 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
S100 protein binding
Specific Function:
Plays an important role in the regulation of cell survival, cell division, angiogenesis, cell differentiation and cell migration. Functions as potent mitogen in vitro.
Gene Name:
FGF1
Uniprot ID:
P05230
Molecular Weight:
17459.58 Da
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:16300395 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23