DT-Web

DB01025 - Amlexanox


Identification
Name Amlexanox
Accession Number DB01025 (APRD00795)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 298.2934
Groups approved
Monoisotopic Weight 298.095356946
Pharmacology
Indication Used as a paste in the mouth to treat aphthous ulcers (canker sores).
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.
Absorption No significant absorption directly through the active ulcer. Most of the systemic absorption is via the gastrointestinal tract.
Protein binding Not Available
Biotransformation Metabolized to hydroxylated and conjugated metabolites.
Route of elimination Not Available
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions Not Available
Food Interactions Not Available

Targets


Protein S100-A12
Name Protein S100-A12
Gene Name S100A12
Pharmacological action unknown
Actions antagonist
References
  • 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
  • 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
  • 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
DTHybrid score 0.9682
Protein S100-A13
Name Protein S100-A13
Gene Name S100A13
Pharmacological action unknown
Actions antagonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.9675
Interleukin-3
Name Interleukin-3
Gene Name IL3
Pharmacological action unknown
Actions antagonist
References
  • 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
  • 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
DTHybrid score 0.9579
Fibroblast growth factor 1
Name Fibroblast growth factor 1
Gene Name FGF1
Pharmacological action unknown
Actions inhibitor
References
  • 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
DTHybrid score 1.1967

Predictions


Id Partner name Gene Name Score
6097 Protein S100-A2 S100A2 0.235
1810 Protein S100-A1 S100A1 0.2342
2132 Protein S100-B S100B 0.1528
1943 Hepatocyte growth factor HGF 0.106
2654 Complement control protein C3L 0.0975
2805 Heparan sulfate glucosamine 3-O-sulfotransferase 3A1 HS3ST3A1 0.088
1525 Heparin-binding growth factor 2 FGF2 0.0864
492 Histamine H1 receptor HRH1 0.0775
361 Fibroblast growth factor 4 FGF4 0.066
4512 Cytochrome P450 3A4 CYP3A4 0.0548
2450 Tyrosine-protein kinase ITK/TSK ITK 0.0138
3856 Fibroblast growth factor receptor 3 FGFR3 0.0131
26 Vascular endothelial growth factor receptor 3 FLT4 0.0101
950 Alpha platelet-derived growth factor receptor PDGFRA 0.01
32 Vascular endothelial growth factor receptor 1 FLT1 0.01
228 Beta platelet-derived growth factor receptor PDGFRB 0.0088
504 Mast/stem cell growth factor receptor KIT 0.0087
407 Vascular endothelial growth factor receptor 2 KDR 0.0086
6022 UDP-glucuronosyltransferase 1-1 UGT1A1 0.0058
4545 Molybdopterin-converting factor subunit 2 moaE 0.0055
4037 Hypothetical protein GPX1 0.0055
4297 Hypothetical protein SP_1951 0.0055
4521 Hypothetical protein BC_2969 0.0055
4540 Hypothetical protein TM_1070 0.0055
4555 Hypothetical protein MT1739 0.0055
4569 Hypothetical protein mshD 0.0055
4578 Hypothetical protein PA3270 0.0055
4747 Hypothetical protein PA3967 0.0055
5177 Hypothetical protein TM_0096 0.0055
5194 Hypothetical protein PA1204 0.0055
5240 Hypothetical protein Rv2991 0.0055
5370 Hypothetical protein TM_1158 0.0055
5710 Hypothetical protein Tb927.5.1360 0.0055
4106 Guanylate kinase GUK1 0.0055
4516 Guanylate kinase gmk 0.0055
4527 Putative hydrolase ycdX ycdX 0.0055
4536 Transcriptional regulator, IclR family TM_0065 0.0055
4546 Aminotransferase, putative TM_1131 0.0055
2501 Protein ygbM ygbM 0.0055
4514 Citrate lyase beta subunit-like protein citE 0.0055
4781 Citrate lyase beta subunit-like protein DR_1240 0.0055
4548 Gyrase B gyrB 0.0055
4526 Oligopeptide ABC transporter, periplasmic oligopeptide-binding protein TM_1223 0.0055
4524 Mannose-6-phosphate isomerase yvyI 0.0055
4535 Glutaconyl-CoA decarboxylase subunit alpha gcdA 0.0055
4522 Arginine N-succinyltransferase subunit alpha astA 0.0055
4547 Iron binding protein FbpA fbpA 0.0055
4538 Hypothetical protein VC1899 VC_1899 0.0055
4529 Oxalate decarboxylase oxdC oxdC 0.0055
658 Para-aminobenzoate synthase component 1 pabB 0.0055
4515 Peripheral plasma membrane protein CASK CASK 0.0055
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0052
4496 C-terminal-binding protein 1 CTBP1 0.005
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0049
3261 Signal recognition particle protein ffh 0.0048
4517 Probable butyrate kinase 2 buk2 0.0048
4533 Glyoxalase family protein BC_1747 0.0048
4528 Phenazine biosynthesis protein PhzD phzD1 0.0048
3759 Glutathione S-transferase gst 0.0048
4541 Glutathione S-transferase GST 0.0048
3237 Beta-lactamase OXA-2 bla 0.0048
56 Delta-aminolevulinic acid dehydratase ALAD 0.0048
2356 Delta-aminolevulinic acid dehydratase hemB 0.0048
3613 Delta-aminolevulinic acid dehydratase hemB 0.0048
3674 Delta-aminolevulinic acid dehydratase hemB 0.0048
4542 Glutaminase 1 glsA1 0.0048
4544 Glutaminase 1 glsA1 0.0048
2929 (S)-2-haloacid dehalogenase dhlB 0.0048
2995 (S)-2-haloacid dehalogenase Not Available 0.0048
4532 Gephyrin GPHN 0.0048
2230 Catalase CAT 0.0045
3249 Catalase katA 0.0045
3625 Catalase katA 0.0045
4539 Catalase katA 0.0045
4941 Catalase katB 0.0045
2775 Dihydroorotate dehydrogenase pyrD 0.0044
4531 Putative ketoacyl reductase actIII 0.0044
3583 6-phosphogluconolactonase pgl 0.0044
3467 Methylglyoxal synthase mgsA 0.0044
2525 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0042
3201 3-phosphoshikimate 1-carboxyvinyltransferase aroA 0.0042
4924 Cytochrome P450 2C8 CYP2C8 0.004
2688 Peptide deformylase def 0.004
2708 Peptide deformylase def 0.004
3004 Peptide deformylase def 0.004
4337 Peptide deformylase def 0.004
4338 Peptide deformylase def 0.004
5368 Peptide deformylase def 0.004
5371 Peptide deformylase def 0.004
6375 Peptide deformylase def 0.004
6378 Peptide deformylase def 0.004
6379 Peptide deformylase def 0.004
6776 Peptide deformylase def 0.004
6900 Peptide deformylase def 0.004
4534 Cytohesin-2 CYTH2 0.004
4269 Hypoxanthine-guanine phosphoribosyltransferase, putative HGPRTase 0.0038
2548 Subtilisin Carlsberg apr 0.0038
4200 Cytochrome P450 1A2 CYP1A2 0.0038
1588 Multidrug resistance protein 1 ABCB1 0.0038
4119 Cytochrome P450 2D6 CYP2D6 0.0036
810 Heme oxygenase 1 HMOX1 0.0033
3391 Heme oxygenase 1 pbsA1 0.0033
3027 Streptavidin Not Available 0.0032
500 Monocarboxylate transporter 4 SLC16A3 0.0031
76 Nitric-oxide synthase, brain NOS1 0.0028
5682 Ribonuclease pancreatic RNASE1 0.0028
357 Carbonic anhydrase 2 CA2 0.0021
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