Amlexanox

Amlexanox

File:Amlexanox.svg
Clinical data
Trade names	Aphthasol
AHFS/Drugs.com	Monograph
MedlinePlus	a601017
Routes of administration	Topical
ATC code	A01AD07 (WHO) R03DX01 (WHO)
Pharmacokinetic data
Elimination half-life	3.5 hours
Excretion	Renal (17%)
Identifiers
IUPAC name 2-amino-7-isopropyl-5-oxo-5H-chromeno[2,3-b]pyridine-3-carboxylic acid
CAS Number	68302-57-8 checkY
PubChem CID	2161
IUPHAR/BPS	7113
DrugBank	DB01025 checkY
ChemSpider	2076 checkY
UNII	BRL1C2459K
KEGG	D01828 checkY
ChEBI	CHEBI:31205 checkY
ChEMBL	ChEMBL1096 checkY
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}}
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C16H14N2O4
Molar mass	298.298 g·mol−1
3D model (JSmol)	Interactive image
SMILES O=C1c3cc(ccc3Oc2nc(c(cc12)C(=O)O)N)C(C)C
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) checkY Key:SGRYPYWGNKJSDL-UHFFFAOYSA-N checkY
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Amlexanox (trade name Aphthasol) is an anti-inflammatory antiallergic immunomodulator used to treat recurrent aphthous ulcers (canker sores), and (in Japan) several inflammatory conditions. This drug has been discontinued in the U.S.

Medical uses

Amlexanox is the active ingredient in a common topical treatment for recurrent aphthous ulcers of the mouth (canker sores), reducing both healing time and pain. Amlexanox 5% paste is well tolerated, and is typically applied four times per day directly on the ulcers. A 2011 review found it to be the most effective treatment of the eight treatments investigated for recurrent canker sores. It is also used to treat ulcers associated with Behçet disease.

In Japan, it is used to treat bronchial asthma, allergic rhinitis and conjunctivitis.

Contraindications

The drug is contraindicated in those with known allergies to it.

Adverse effects

Amlexanox may cause a slightly painful stinging or burning sensation, nausea or diarrhea.

Mechanism of action

Its mechanism of action is not well-determined, but it might inhibit inflammation by inhibiting the release of histamine and leukotrienes. It has been shown to selectively inhibit TBK1 and IKK-ε, producing reversible weight loss and improved insulin sensitivity, reduced inflammation and attenuated hepatic steatosis without affecting food intake in obese mice. It produced a statistically significant reduction in glycated hemoglobin and fructosamine in obese patients with type 2 diabetes and nonalcoholic fatty liver disease

Chemistry

The chemical itself is an odorless, white to yellowish-white powder.

The 5% preparation for patient use is an adherent beige paste, and it is also available in some countries as a tablet that adheres to the ulcer in the mouth.

Pharmacokinetics

Amlexanox applied to an aphthous ulcer is largely absorbed through the gastrointestinal tract; an insignificant amount enters the bloodstream through the ulcer itself. After a single 100 mg dose, mean maximum serum concentration occurs 2.4 +/- 0.9 hours after application, with a half-life of elimination (through urine) of 3.5 +/- 1.1 hours. With multiple daily applications (four doses per day), steady state serum levels occur after one week, with no accumulation occurring after four weeks.

History

The patent for its use as a treatment for aphthous ulcers was issued in November 1994 to inventors Kakubhai R. Vora, Atul Khandwala and Charles G. Smith, and assigned to Chemex Pharmaceuticals, Inc.

Society and culture

Economics

A 2011 review found a one-week supply of amlexanox 5% paste to cost $30.

Research

A review found that, as of July 2011, robust studies investigating its effectiveness alongside other canker sore treatments were still needed.

Because it is an inhibitor of the protein kinases TBK1 and IKK-ε, which are implicated in the etiology of type II diabetes and obesity, amlexanox may be a candidate for human clinical trials testing in relation to these diseases.

Synthesis

File:Amlexanoxsynthesis.png

Amlexanox synthesis: