Identification

Name
Amlexanox
Accession Number
DB01025  (APRD00795)
Type
Small Molecule
Groups
Approved, 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
  • 2-Amino-7-isopropyl-5-oxo-5H-(1)benzopyrano(2,3-b)pyridine-3-carboxylic acid
  • Amlexanox
  • Amlexanoxo
  • Amlexanoxum
  • Amoxanox
External IDs
AA-673 / CHX 3673 / CHX-3673
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AptheraPaste5 %OralPharmascience IncNot applicableNot applicableCanada
International/Other Brands
Aphthasol / Elics / OraDisc A / Solfa
Categories
UNII
BRL1C2459K
CAS number
68302-57-8
Weight
Average: 298.2934
Monoisotopic: 298.095356946
Chemical Formula
C16H14N2O4
InChI Key
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

Pharmacology

Indication

Used as a paste in the mouth to treat aphthous ulcers (canker sores).

Structured Indications
Not Available
Pharmacodynamics

Amlexanox 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 action

As 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.

TargetActionsOrganism
UProtein S100-A12
antagonist
Human
UProtein S100-A13
antagonist
Human
UInterleukin-3
antagonist
Human
UFibroblast growth factor 1
inhibitor
Human
Absorption

No significant absorption directly through the active ulcer. Most of the systemic absorption is via the gastrointestinal tract.

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Metabolized to hydroxylated and conjugated metabolites.

Route of elimination
Not Available
Half life

Elimination half-life is 3.5 ± 1.1 hours.

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
No interactions found.
Food Interactions
Not Available

References

Synthesis Reference
Not 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
Human Metabolome Database
HMDB15160
KEGG Drug
D01828
PubChem Compound
2161
PubChem Substance
46504508
ChemSpider
2076
ChEBI
31205
ChEMBL
CHEMBL1096
Therapeutic Targets Database
DAP000321
PharmGKB
PA164745310
HET
ANW
Drugs.com
Drugs.com Drug Page
ATC Codes
A01AD07 — AmlexanoxR03DX01 — Amlexanox
AHFS Codes
Not Available
PDB Entries
Not Available
FDA label
Download (129 KB)
MSDS
Download (79.7 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2Active Not RecruitingTreatmentBMI >30 kg/m2 / Non Alcoholic Fatty Liver Diseases (NAFLD) / Type 2 Diabetes Mellitus1
2CompletedTreatmentBMI >30 kg/m2 / Non-Alcoholic Fatty Liver Disease (NAFLD) / Type 2 Diabetes Mellitus1
2CompletedTreatmentOral Mucositis1

Pharmacoeconomics

Manufacturers
Not 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)
US5362737No1994-11-082011-11-08Us

Properties

State
Solid
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0091000000-00993cade43b41e35544

Taxonomy

Description
This compound belongs to the class of organic compounds known as chromeno[2,3-b]pyridine-5-ones. These are compounds containing a Chromeno[2,3-b]pyridine moiety that carries an oxo group at the 5-position.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Benzopyrans
Sub Class
1-benzopyrans
Direct Parent
Chromeno[2,3-b]pyridine-5-ones
Alternative Parents
Chromenopyridines / Pyranopyridines / Pyridinecarboxylic acids / Pyranones and derivatives / Aminopyridines and derivatives / Benzenoids / Imidolactams / Vinylogous amides / Heteroaromatic compounds / Amino acids
show 9 more
Substituents
Chromeno[2,3-b]pyridine-5-one / Chromenopyridine / Pyranopyridine / Pyridine carboxylic acid / Pyridine carboxylic acid or derivatives / Aminopyridine / Pyranone / Pyran / Pyridine / Benzenoid
show 20 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid, pyridochromene (CHEBI:31205)

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 recruitme...
Gene Name
S100A12
Uniprot ID
P80511
Uniprot Name
Protein S100-A12
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 doe...
Gene Name
S100A13
Uniprot ID
Q99584
Uniprot Name
Protein S100-A13
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 blo...
Gene Name
IL3
Uniprot ID
P08700
Uniprot Name
Interleukin-3
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
Uniprot Name
Fibroblast growth factor 1
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]

Drug created on June 13, 2005 07:24 / Updated on October 02, 2017 04:51