Amlexanox

Summary

Amlexanox (CHEMBL1096) is an approved small-molecule anti-allergic agent (ATC A01AD07) targeting IKBKE and TBK1; indicated across 2 conditions including obstructive lung disease and stomatitis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: A01AD07 (+1 more)
• Targets: 2 (IKBKE, TBK1)
• Indications: 2 conditions
• Clinical trials: 3
• Chemistry: 298.29 Da · C16H14N2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL1096
Name	Amlexanox
Type	Small molecule
Max phase	4
FDA approved	no
PubChem CID	2161
ChEBI	CHEBI:31205
ATC	A01AD07, R03DX01
Molecular formula	C16H14N2O4
Molecular weight	298.29
InChIKey	SGRYPYWGNKJSDL-UHFFFAOYSA-N

SMILES: CC(C)C1=CC2=C(C=C1)OC3=NC(=C(C=C3C2=O)C(=O)O)N

IUPAC name: 2-amino-5-oxo-7-propan-2-ylchromeno[2,3-b]pyridine-3-carboxylic acid

ChEBI definition: A pyridochromene-derived monocarboxylic acid having an amino substituent at the 2-position, an oxo substituent at the 5-position and an isopropyl substituent at the 7-position.

Pharmacological roles (ChEBI): anti-allergic agent, anti-ulcer drug, non-steroidal anti-inflammatory drug.

Also known as: AA-673, Amlexanox, Amlexanoxo, Amoxanox, Aphthasol, Aphtheal, CHX 3673, CHX-3673, Elics, Solfa, SID26719859, SID50112726

Patent coverage: 1,257 distinct patent families (4,195 SureChEMBL compound mentions), from 3 matched compound structure(s). One matched structure accounts for 4,126 (98%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
IKBKE	inhibitor of nuclear factor kappa B kinase subunit epsilon	Inhibition	6	0.3%	Q14164
TBK1	TANK binding kinase 1	Inhibition	6	0.7%	Q9UHD2

Broader ChEMBL bioactivity targets: 19 (assay-derived). Sample: Pyruvate kinase PKM, Lysine-specific demethylase 4E, Nuclear receptor ROR-gamma, Fructose-bisphosphate aldolase, G-protein coupled receptor 35, NPC intracellular cholesterol transporter 1, Ras-related protein Rab-9A, ATP-binding cassette sub-family C member 4, Alpha-1A adrenergic receptor, Delta-type opioid receptor.

Bioactivity

ChEMBL activities: 15 potent at pChembl ≥ 5 of 27 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
NPC1	6.5	Potency	316.2	nM	CHEMBL_ACT_4744305
RAB9A	6.3	Potency	501.2	nM	CHEMBL_ACT_3854601
TBK1	6.07	IC50	850	nM	CHEMBL_ACT_18811314
TBK1	6.07	IC50	851.1	nM	CHEMBL_ACT_18811346
TBK1	6.01	IC50	980	nM	CHEMBL_ACT_27401006
ABCC4	5.66	IC50	2200	nM	CHEMBL_ACT_18130895
GPR35	5.4	EC50	4000	nM	CHEMBL_ACT_18198030
P51450	5.4	Potency	3981	nM	CHEMBL_ACT_4094663
IKBKE	5.29	IC50	5100	nM	CHEMBL_ACT_18811456
IKBKE	5.29	IC50	5129	nM	CHEMBL_ACT_18811488
Q27686	5.15	Potency	7080	nM	CHEMBL_ACT_3908021
Q27686	5.15	Potency	7080	nM	CHEMBL_ACT_4282771
P51450	5.1	Potency	7943	nM	CHEMBL_ACT_4778974
Q8VEB1	5.05	IC50	8860	nM	CHEMBL_ACT_25578777
P51450	5	Potency	10000	nM	CHEMBL_ACT_4778220

Target pathways

Aggregated over 2 target gene(s): IKBKE, TBK1.

Top Reactome pathways

50 total, by targets touching each:

Pathway	Targets	Genes
TNFR1-induced proapoptotic signaling	2	IKBKE, TBK1
Regulation of TNFR1 signaling	2	IKBKE, TBK1
TICAM1-dependent activation of IRF3/IRF7	2	IKBKE, TBK1
TRAF3-dependent IRF activation pathway	2	IKBKE, TBK1
TRAF6 mediated IRF7 activation	2	IKBKE, TBK1
Negative regulators of DDX58/IFIH1 signaling	2	IKBKE, TBK1
Activation of IRF3, IRF7 mediated by TBK1, IKKε (IKBKE)	2	IKBKE, TBK1
SARS-CoV-1 activates/modulates innate immune responses	2	IKBKE, TBK1
SARS-CoV-2 activates/modulates innate and adaptive immune responses	2	IKBKE, TBK1
Regulation of TBK1, IKKε (IKBKE)-mediated activation of IRF3, IRF7	2	IKBKE, TBK1
Regulation of TBK1, IKKε-mediated activation of IRF3, IRF7 upon TLR3 ligation	2	IKBKE, TBK1
Cytokine Signaling in Immune system	1	TBK1
ZBP1(DAI) mediated induction of type I IFNs	1	TBK1
IRF3 mediated activation of type 1 IFN	1	TBK1
Signal Transduction	1	TBK1
Macroautophagy	1	TBK1
Disease	1	TBK1
Toll Like Receptor 4 (TLR4) Cascade	1	TBK1
MyD88-independent TLR4 cascade	1	TBK1
Toll Like Receptor 3 (TLR3) Cascade	1	TBK1
Innate Immune System	1	TBK1
Immune System	1	TBK1
Toll-like Receptor Cascades	1	TBK1
DDX58/IFIH1-mediated induction of interferon-alpha/beta	1	TBK1
STING mediated induction of host immune responses	1	TBK1
Cytosolic sensors of pathogen-associated DNA	1	TBK1
Regulation of innate immune responses to cytosolic DNA	1	TBK1
STAT6-mediated induction of chemokines	1	TBK1
IRF3-mediated induction of type I IFN	1	TBK1
Interleukin-1 family signaling	1	TBK1

Dominant GO biological processes

GO term	Targets
activation of innate immune response	2
positive regulation of type I interferon production	2
positive regulation of canonical NF-kappaB signal transduction	2
defense response to virus	2
type I interferon-mediated signaling pathway	2
positive regulation of type I interferon-mediated signaling pathway	2
protein phosphorylation	2
response to stress	2
immune response	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
gene expression	1
positive regulation of lipid storage	1
response to interferon-beta	1
regulation of protein-containing complex assembly	1
mRNA stabilization	1

Indications & clinical

Indications

2 indications (1 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
obstructive lung disease	4	MONDO:0002267	HP:0006536
stomatitis	2	MONDO:0004842	EFO:1001904

Clinical trials

Total trials: 3.

Phase distribution

Phase	Trials
PHASE2	3

Top trials by phase / activity

NCT	Phase	Status	Title
NCT01083875	PHASE2	COMPLETED	Study to Determine the Effects Treatment With Amlexanox 0.5% Oral Rinse Solution on Oral Mucositis Associated With Radiation Therapy for Cancer of the Head and Neck Region
NCT01842282	PHASE2	TERMINATED	Amlexanox for Type 2 Diabetes and Obesity
NCT01975935	PHASE2	COMPLETED	Efficacy of Amlexanox vs. Placebo in Type 2 Diabetic Patients

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline or drug-level clinical/variant annotations in PharmGKB for this molecule.

Related molecules

Related molecules

Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.

53 molecules share ≥1 primary target. Top 53 by shared-target count:

Molecule	Source	Status	Shared targets
CRIZOTINIB	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
Entrectinib	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
Erlotinib	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
FEDRATINIB	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
FOSTAMATINIB	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
MOMELOTINIB	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
RUXOLITINIB	ChEMBL + PubChem	Phase 4 (approved)	IKBKE, TBK1
BOSUTINIB	ChEMBL	Phase 4 (approved)	IKBKE, TBK1
MIDOSTAURIN	ChEMBL	Phase 4 (approved)	IKBKE, TBK1
NINTEDANIB	ChEMBL	Phase 4 (approved)	IKBKE, TBK1
PACRITINIB	ChEMBL	Phase 4 (approved)	IKBKE, TBK1
SUNITINIB	ChEMBL	Phase 4 (approved)	IKBKE, TBK1
ALVOCIDIB	ChEMBL	Phase 3	IKBKE, TBK1
DOVITINIB	ChEMBL	Phase 3	IKBKE, TBK1
LESTAURTINIB	ChEMBL	Phase 3	IKBKE, TBK1
ORANTINIB	ChEMBL	Phase 3	IKBKE, TBK1
ADAVOSERTIB	ChEMBL	Phase 2	IKBKE, TBK1
AT-9283	ChEMBL	Phase 2	IKBKE, TBK1
CENISERTIB	ChEMBL	Phase 2	IKBKE, TBK1
FORETINIB	ChEMBL	Phase 2	IKBKE, TBK1
MILCICLIB	ChEMBL	Phase 2	IKBKE, TBK1
R-406	ChEMBL	Phase 2	IKBKE, TBK1
SU-014813	ChEMBL	Phase 2	IKBKE, TBK1
TOZASERTIB	ChEMBL	Phase 2	IKBKE, TBK1
UCN-01	ChEMBL	Phase 2	IKBKE, TBK1
Afatinib	PubChem	Approved	IKBKE, TBK1
Binimetinib	PubChem	Approved	IKBKE, TBK1
Cabozantinib	PubChem	Approved	IKBKE, TBK1
Capmatinib	PubChem	Approved	IKBKE, TBK1
Cobimetinib	PubChem	Approved	IKBKE, TBK1
dacomitinib	PubChem	Approved	IKBKE, TBK1
Gefitinib	PubChem	Approved	IKBKE, TBK1
Ibrutinib	PubChem	Approved	IKBKE, TBK1
Idelalisib	PubChem	Approved	IKBKE, TBK1
Lapatinib	PubChem	Approved	IKBKE, TBK1
Pazopanib	PubChem	Approved	IKBKE, TBK1
Pexidartinib	PubChem	Approved	IKBKE, TBK1
Ponatinib	PubChem	Approved	IKBKE, TBK1
Quizartinib	PubChem	Approved	IKBKE, TBK1
regorafenib	PubChem	Approved	IKBKE, TBK1
Selumetinib	PubChem	Approved	IKBKE, TBK1
Sorafenib	PubChem	Approved	IKBKE, TBK1
Tepotinib	PubChem	Approved	IKBKE, TBK1
Tirbanibulin	PubChem	Approved	IKBKE, TBK1
Tovorafenib	PubChem	Approved	IKBKE, TBK1
Trametinib	PubChem	Approved	IKBKE, TBK1
FILGOTINIB	ChEMBL	Phase 4 (approved)	TBK1
GILTERITINIB	ChEMBL	Phase 4 (approved)	IKBKE
RUBOXISTAURIN	ChEMBL	Phase 3	TBK1
CERDULATINIB	ChEMBL	Phase 2	TBK1
ILORASERTIB	ChEMBL	Phase 2	IKBKE
SILMITASERTIB	ChEMBL	Phase 2	TBK1
Capivasertib	PubChem	Approved	IKBKE